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This research examined the impact of exogenous thermophilic bacteria and ripening agents on greenhouse gas (GHG) emission, enzyme activity, and microbial community during composting. The use of ripening agents alone resulted in a 30.9 % reduction in CO2 emissions, while the use of ripening agents and thermophilic bacteria resulted in a 50.8 % reduction in N2O emissions. Pearson's analysis showed that organic matter and nitrate nitrogen were the key parameters affecting GHG emissions. There was an inverse correlation between CO2 and CH4 releases and methane monooxygenase α subunit and N2O reductase activity (P<0.05). Additionally, N2O emissions were positively related to ß-1, 4-N-acetylglucosaminidase, and ammonia monooxygenase activity (P<0.05). Deinococcota, Chloroflexi, and Bacteroidota are closely related to CO2 and N2O emissions. Overall, adding thermophilic bacteria represents an effective strategy to mitigate GHG emissions during composting.
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Bactérias , Compostagem , Gases de Efeito Estufa , Bactérias/metabolismo , Compostagem/métodos , Dióxido de Carbono , Metano/metabolismo , Óxido Nitroso/metabolismo , Microbiologia do Solo , Microbiota/fisiologia , Solo/químicaRESUMO
Ulcerative colitis (UC) is a chronic non-specific colitis disease. In recent years, fecal microbiota transplantation (FMT), including improved washed microbiota transplantation (WMT), and biological agents have helped improve the prognosis of patients with UC. However, a significant number of patients with moderate to severe UC do not get relief from glucocorticoids, immunosuppressants, and TNF-α antagonists. Patients with severe UC are frequently burdened with opportunistic infections and subsequent surgical interventions. Combined treatment modalities are crucial for patients with severe UC and opportunistic infections. Herein, we reported a case of a 25-year-old female with refractory severe UC complicated with recurrent Clostridioides difficile infection and recurrent cytomegalovirus infection for six years. Surgical removal of the affected bowel segment was almost unavoidable. She showed endoscopic and histological recovery after comprehensive WMT and Vedolizumab treatment. The following are our learnings from the case: 1. A combination of WMT and biological agents can potentially obviate the necessity for surgical treatment in patients with refractory severe UC and promote histological remission. 2. Personalized comprehensive treatment and chronic disease management models for patients with UC should be emphasized. 3. WMT can help treat opportunistic infections, which may also strengthen the treatment with gut-targeted biological agents when traditional TNF-α antagonists show poor efficacy.
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The effects and mitigation mechanisms of biochar added at different composting stages on N2O emission were investigated. Four treatments were set as follows: CK: control, BB10%: +10 % biochar at beginning of composting, BB5%&T5%: +5% biochar at beginning and + 5 % biochar after thermophilic stage of composting, BT10%: +10 % after thermophilic stage of composting. Results showed that treatment BB10%, BB5%&T5%, and BT10% reduced total N2O emissions by 55 %, 37 %, and 36 %, respectively. N2O emission was closely related to most physicochemical properties, while it was only related to amoA gene and hydroxylamine oxidoreductase. Different addition strategies of biochar changed the contributions of physicochemical properties, functional genes and enzymes to N2O emission. Organic matter and C/N contributed 23.7 % and 27.6 % of variations in functional gene abundances (P < 0.05), respectively. pH and C/N (P < 0.05) contributed 37.3 % and 17.3 % of variations in functional enzyme activities. These findings provided valuable insights into mitigating N2O emissions during composting.
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Agricultura , Carvão Vegetal , Compostagem , Óxido Nitroso , Carvão Vegetal/química , Compostagem/métodos , Óxido Nitroso/análise , Agricultura/métodos , Solo/químicaRESUMO
A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-ß-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.
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Herein we have pioneered an innovative synthetic strategy for the efficient assembly of various heteroarene-condensed benzofuran derivatives, utilizing benzofuran-derived azadienes (BDAs) and quinolines as the starting materials. This method functions with transition-metal catalysis and uses cost-effective formic acid as the reducing agent. Mechanistic investigations indicate that this transformation would involve a [4 + 2] annulation cascade process. This approach demonstrates a high tolerance to various functional groups and yields excellent results.
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BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Fator de Transcrição STAT3 , Humanos , Camundongos , Animais , Colite Ulcerativa/terapia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ácidos Graxos Voláteis/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Bactérias/metabolismo , Modelos Animais de Doenças , Inflamação , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Colo , Proteína Forkhead Box O3/metabolismoRESUMO
Aging and genetic-related disorders in the human brain lead to impairment of daily cognitive functions. Due to their neural synaptic complexity and the current limits of knowledge, reversing these disorders remains a substantial challenge for brain-computer interfaces (BCI). In this work, a solution is provided to potentially override aging and neurological disorder-related cognitive function loss in the human brain through the application of the authors' quantum synaptic device. To illustrate this point, a quantum topological insulator (QTI) Bi2Se2Te-based synaptic neuroelectronic device, where the electric field-induced tunable topological surface edge states and quantum switching properties make them a premier option for establishing artificial synaptic neuromodulation approaches, is designed and developed. Leveraging these unique quantum synaptic properties, the developed synaptic device provides the capability to neuromodulate distorted neural signals, leading to the reversal of age-related disorders via BCI. With the synaptic neuroelectronic characteristics of this device, excellent efficacy in treating cognitive neural dysfunctions through modulated neuromorphic stimuli is demonstrated. As a proof of concept, real-time neuromodulation of electroencephalogram (EEG) deduced distorted event-related potentials (ERP) is demonstrated by modulation of the synaptic device array.
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Interfaces Cérebro-Computador , Teoria Quântica , Humanos , Sinapses/fisiologia , Eletroencefalografia , Encéfalo/fisiologia , Potenciais Evocados/fisiologia , EletrônicaRESUMO
BACKGROUND: Probiotics are a potentially effective therapy for inflammatory bowel disease (IBD); IBD is linked to impaired gut microbiota and intestinal immunity. However, the utilization of an antibiotic cocktail (Abx) prior to the probiotic intervention remains controversial. This study aims to identify the effect of Abx pretreatment from dextran sulfate sodium (DSS)-induced colitis and to evaluate whether Abx pretreatment has an enhanced effect on the protection of Clostridium butyricum Miyairi588 (CBM) from colitis. RESULTS: The inflammation, dysbiosis, and dysfunction of gut microbiota as well as T cell response were both enhanced by Abx pretreatment. Additionally, CBM significantly alleviated the DSS-induced colitis and impaired gut epithelial barrier, and Abx pretreatment could enhance these protective effects. Furthermore, CBM increased the benefit bacteria abundance and short-chain fatty acids (SCFAs) level with Abx pretreatment. CBM intervention after Abx pretreatment regulated the imbalance of cytokines and transcription factors, which corresponded to lower infiltration of Th1 and Th17 cells, and increased Th2 cells. CONCLUSIONS: Abx pretreatment reinforced the function of CBM in ameliorating inflammation and barrier damage by increasing beneficial taxa, eliminating pathogens, and inducing a protective Th2 cell response. This study reveals a link between Abx pretreatment, microbiota, and immune response changes in colitis, which provides a reference for the further application of Abx pretreatment before microbiota-based intervention.
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Colite , Doenças Inflamatórias Intestinais , Probióticos , Humanos , Animais , Camundongos , Antibacterianos/efeitos adversos , Células Th2 , Células Th17 , Colite/induzido quimicamente , Colite/prevenção & controle , Probióticos/farmacologia , Inflamação , Imunidade , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Phytoremediation has emerged as a common technique for remediating Cd pollution in farmland soil. Moreover, phosphorus, an essential element for plants, can alter the pectin content of plant cell walls and facilitate the accumulation of Cd in plant tissues, thereby enhancing phytoremediation efficiency. Therefore, pot experiments were conducted in order to investigate the effect of phosphorus levels on Cd extraction, phosphorus transformation and phosphorus-related genes during phytoremediation. The results revealed that an optimal application of suitable phosphate fertilizers elevated the soil's pH and electrical conductivity (EC), facilitated the conversion of soil from insoluble phosphorus into available forms, augmented the release of pertinent enzyme activity, and induced the expression of phosphorus cycling-related genes. These enhancements in soil conditions significantly promoted the growth of ryegrass. When applying phosphorus at a rate of 600 mg/kg, ryegrass exhibited plant height, dry weight, and chlorophyll relative content that were 1.27, 1.26, and 1.18 times higher than those in the control group (P0), while the Cd content was 1.12 times greater than that of P0. The potentially toxic elements decline ratio and bioconcentration factor were 42.86% and 1.17 times higher than those of P0, respectively. Consequently, ryegrass demonstrated the highest Cd removal efficiency under these conditions. Results from redundancy analysis (RDA) revealed a significant correlation among pH, total phosphorus, heavy metal content, phosphorus forms, soil enzyme activity, and phosphorus-related genes. In conclusion, this study suggests applying an optimal amount of suitable phosphate fertilizers can enhance restoration efficiency, leading to a reduction in soil Cd content and ultimately improving the safety of crop production in farmlands.
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Biodegradação Ambiental , Cádmio , Lolium , Fósforo , Poluentes do Solo , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Cádmio/metabolismo , Fósforo/metabolismo , Fósforo/análise , Lolium/metabolismo , Lolium/genética , Lolium/crescimento & desenvolvimento , Fertilizantes/análise , Solo/químicaRESUMO
Introduction: Understanding the gut microbiota and antibiotic resistance gene (ARG) profiles in non-human primates (NHPs) is crucial for evaluating their potential impact on human health and the environment. Methods: In this study, we performed metagenomic analysis of 203 primate fecal samples, including nine NHP species and humans, to comprehensively characterize their gut microbiota and ARGs. Results: Our study reveals the prevailing phyla in primates as Firmicutes, Bacteroidetes, Euryarchaeota, and Proteobacteria. The captive NHPs exhibited higher ARG abundance compared to their wild counterparts, with tetracycline and beta-lactam resistance genes prevailing. Notably, ARG subtypes in Trachypithecus leucocephalus (T. leucocephalus) residing in karst limestone habitats displayed a more dispersed distribution compared to other species. Interestingly, ARG profiles of NHPs clustered based on geographic location and captivity status. Co-occurrence network analysis revealed intricate correlations between ARG subtypes and bacterial taxa. Procrustes analysis unveiled a significant correlation between ARGs and microbial phylogenetic community structure. Taxonomic composition analysis further highlighted differences in microbial abundance among NHPs and humans. Discussion: Our study underscores the impact of lifestyle and geographical location on NHP gut microbiota and ARGs, providing essential insights into the potential risks posed by NHPs to antibiotic resistance dissemination. This comprehensive analysis enhances our understanding of the interplay between NHPs and the gut resistome, offering a critical reference for future research on antibiotic resistance and host-microbe interactions.
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BACKGROUND: The vaginal microbiome is a dynamic community of microorganisms in the vagina. Its alteration may be influenced by multiple factors, including gestational status, menstrual cycle, sexual intercourse, hormone levels, hormonal contraceptives, and vaginal drug administration. Povidone iodine has been used before delivery to reduce infection that may be caused by the ascendance of pathogenic and opportunistic bacteria from the vagina to the uterus. This study aimed to elucidate the impact of povidone iodine use during delivery on the vaginal microbiome. METHODS: This study enrolled a total of 67 women from maternity services in three hospitals. During the delivery process, we have applied povidone iodine in three doses such as low dose, medium dose, and high dose based on the amount of povidone iodine administered, thus, we studied the three groups of women based on the doses applied. Vaginal swab samples were collected both before and immediately after delivery, and the microbial communities were characterized using 16 S rRNA sequencing. The identification of differentially abundant microbial taxa was performed using ZicoSeq software. RESULTS: Before delivery, the vaginal microbiome was dominated by the genus Lactobacillus, with different percentage observed (86.06%, 85.24%, and 73.42% for the low, medium, and high dose groups, respectively). After delivery, the vaginal microbial community was restructured, with a significant decrease in the relative abundance of Lactobacillus in all three groups (68.06%, 50.08%, and 25.89%), and a significant increase in alpha diversity across all 3 groups (P < 0.01). Furthermore, as the dose of povidone iodine used during delivery increased, there was a corresponding decrease in the relative abundance of Lactobacillus (P < 0.01). Contrary, there was an increase in microbial diversity and the relative abundances of Pseudomonas (0.13%, 0.26%, and 13.04%, P < 0.01) and Ralstonia (0.01%, 0.02%, and 16.07%, P < 0.01) across the groups. Notably, some functional metabolic pathways related to sugar degradation were observed to have significant change with increasing use of povidone iodine. CONCLUSION: Povidone iodine was associated with the vaginal microbiome alterations after parturition, and its significant change was associated to the dosage of povidone iodine administered. The escalation in iodine dosage was linked to a decrease in Lactobacilli abundance, and elevated prevalence of Pseudomonas and Ralstonia. There is a need for longitudinal studies to clearly understanding the effect of povidone iodine use on maternal and infant microbiome.
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Microbiota , Povidona-Iodo , Feminino , Humanos , Gravidez , Povidona-Iodo/farmacologia , Vagina/microbiologia , Microbiota/genética , Bactérias/genética , Ciclo Menstrual , RNA Ribossômico 16S/genéticaRESUMO
Nitrous oxide (N2O) production is associated with ammonia-oxidizing bacteria (amoA-AOB) and denitrifying fungi (nirK-fungi) during the incorporation of biochar and biogas residue composting. This research examined the relative contribution of alterations in the abundance, diversity and structure of amoA-AOB and nirK-fungi communities on N2O emission by real-time PCR and sequence processing. Results showed that N2O emissions showed an extreme relation with the abundance of amoA-AOB (rs = 0.584) while giving credit to nirK-fungi (rs = 0.500). Nitrosomonas and Nitrosospira emerged as the dominant genera driving ammoxidation process. Biogas residue changed the community structure of AOB by altering Nitrosomonadaceae proportion and physiological capacity. The denitrification process, primarily governed by nirK-fungi, served as a crucial pathway for N2O production, unveiling the pivotal mechanism of biochar to suppress N2O emissions. C/N and NH4+-N were identified as significant parameters influencing the distribution of nirK-fungi, especially Micromonospora, Halomonas and Mesorhizobium.
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Betaproteobacteria , Compostagem , Oryza , Desnitrificação , Oryza/metabolismo , Amônia/metabolismo , Biocombustíveis , Solo/química , Microbiologia do Solo , Óxido Nitroso/análise , Betaproteobacteria/metabolismo , Oxirredução , NitrificaçãoRESUMO
BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single-donor (SD) or multi-donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms. METHODS: Fecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal-chow diet (NCD) or a high-fat diet (HFD) for 3 weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12 weeks. RESULTS: Fecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD-FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD-fed mice. Compared to untreated HFD-fed mice, MD-FMT significantly decreased the relative expression of IL-1ß, IL-6, TNF-α, IFN-γ, and IL-1ß mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin-1, occludin, and E-cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD-FMT intervention. Furthermore, FMT reversed HFD-induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia. CONCLUSION: NAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD-fed controls. MD-FMT restored gut dysbiosis in HFD-fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.
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Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Doenças não Transmissíveis , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Transplante de Microbiota Fecal , Disbiose , Camundongos Endogâmicos C57BL , Fígado/metabolismoRESUMO
BACKGROUND AND AIM: Mucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y-box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution. METHODS: We studied the characteristics of UXT-V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT-V1 in the colonic epithelium was investigated using lentivirus-mediated shRNA in vitro and ex vivo. Through endogenous Co-immunoprecipitation and LC-MS/MS, we identified ZONAB as a UXT-V1-interactive protein. RESULTS: Herein, we report that UXT-V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT-V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT-V1 in NCM-460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT-V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT-V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation-related genes, including AML1 and KLF4. CONCLUSION: Taken together, our study reveals a potential role of UXT-V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Mucosa Intestinal/metabolismo , Diferenciação Celular/genética , Células Epiteliais/metabolismo , Isoformas de Proteínas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Chaperonas Moleculares/metabolismoRESUMO
BACKGROUND: Immunotherapy, including adoptive cell therapy (ACT) and immune checkpoint inhibitors (ICIs), has a limited effect in most patients with colorectal cancer (CRC), and the efficacy is further limited in patients with liver metastasis. Lack of antitumor lymphocyte infiltration could be a major cause, and there remains an urgent need for more potent and safer therapies for CRC. METHODS: In this study, the antitumoral synergism of low molecular weight heparin (LMWH) combined with immunotherapy in the microsatellite stable (MSS) highly aggressive murine model of CRC was fully evaluated. RESULTS: Dual LMWH and ACT objectively mediated the stagnation of tumor growth and inhibition of liver metastasis, neither LMWH nor ACT alone had any antitumoral activity on them. The combination of LMWH and ACT obviously increased the infiltration of intratumor CD8+ T cells, as revealed by multiplex immunohistochemistry, purified CD8+ T-cell transfer assay, and IVIM in vivo imaging. Mechanistically, evaluation of changes in the tumor microenvironment revealed that LMWH improved tumor vascular normalization and facilitated the trafficking of activated CD8+ T cells into tumors. Similarly, LMWH combined with anti-programmed cell death protein 1 (PD-1) therapy provided superior antitumor activity as compared with the single PD-1 blockade in murine CT26 tumor models. CONCLUSIONS: LMWH could enhance ACT and ICIs-based immunotherapy by increasing lymphocyte infiltration into tumors, especially cytotoxic CD8+ T cells. These results indicate that combining LMWH with an immunotherapy strategy presents a promising and safe approach for CRC treatment, especially in MSS tumors.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Linfócitos T CD8-Positivos , Imunoterapia , Neoplasias Colorretais/tratamento farmacológico , Microambiente TumoralRESUMO
Amendments with activators or microorganisms to enhance phytoremediation in toxic-metal-polluted soils have been widely studied. In this research, the production of indoleacetic acid, siderophore, and 1-aminocyclopropane-1-carboxylate (ACC) deaminase by phosphate-solubilizing bacteria was investigated during a pure culture experiment. Pot experiments were performed using Cd-polluted soil with the following treatments: control (CK, only ultrapure water), orange-peel-based activator (OG), and a combination of phosphate-solubilizing bacteria (Acinetobacter pitti) and OG (APOG). Ryegrass plant height and fresh weight, Cd content in ryegrass, total and available Cd soil content, soil enzyme activity, and soil bacterial diversity were determined in this work. The findings showed that the height of ryegrass in OG and APOG increased by 14.78% and 21.23%. In the APOG group, a decreased ratio of Cd was 3.37 times that of CK, and the bioconcentration factor was 1.28 times that of CK. The neutral phosphatase activity of APOG was 1.33 times that of CK and catalase activity was 1.95 times that of CK. The activity of urease was increased by 35.48%. APOG increased the abundance of beneficial bacteria and Proteobacteria was the dominant bacterium, accounting for 57.38% in APOG. Redundancy analysis (RDA) showed that nutrient elements were conducive to the propagation of the dominant bacteria, the secretion of enzymes, and the extraction rate of Cd in the soil. The possible enhancement mechanism of phytoremediation of cadmium by A. pitti combined with OG was that, on the one hand, APOG increased soil nutrient elements and enzyme activities promoted the growth of ryegrass. On the other hand, APOG activated Cd and boosted the movement of Cd from soil to ryegrass. This research offers insight for the combination of phosphate-solubilizing bacteria with an orange-peel-based activator to improve phytoremediation of Cd-contaminated soils and also provides a new way for the resource utilization of fruit residue.
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Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.
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Neuromorphic artificial intelligence systems are the future of ultrahigh performance computing clusters to overcome complex scientific and economical challenges. Despite their importance, the advancement in quantum neuromorphic systems is slow without specific device design. To elucidate biomimicking mammalian brain synapses, a new class of quantum topological neuristors (QTN) with ultralow energy consumption (pJ) and higher switching speed (µs) is introduced. Bioinspired neural network characteristics of QTNs are the effects of edge state transport and tunable energy gap in the quantum topological insulator (QTI) materials. With augmented device and QTI material design, top notch neuromorphic behavior with effective learning-relearning-forgetting stages is demonstrated. Critically, to emulate the real-time neuromorphic efficiency, training of the QTNs is demonstrated with simple hand gesture game by interfacing them with artificial neural networks to perform decision-making operations. Strategically, the QTNs prove the possession of incomparable potential to realize next-gen neuromorphic computing for the development of intelligent machines and humanoids.
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Fused furans are commonly found units in natural products and medicinal molecules, and methods for their introduction are of fundamental importance. Here we report one-pot cycloadditions of ethynyl indoloxazolidones with 1,3-cyclohexanediones enabled by copper catalysis, leading to a series of functionalized furan derivatives in good yields. This method features mild reaction conditions, high efficiency, and wide substrate scope.
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AIMS: The present study aimed to prospectively evaluate the influence of gestational diabetes mellitus (GDM) on the gut microbiota in 1- and 6-month-old offspring, as well as the dynamic changes from 1 to 6 months of age. METHODS: Seventy-three mother-infant dyads (34 GDM vs 39 non-GDM) were included in this longitudinal study. Two fecal samples were collected for each included infant at home by the parents at 1 month of age ("M1 phase") and again at 6 months of age ("M6 phase"). Gut microbiota were profiled by 16S rRNA gene sequencing. RESULTS: Although no significant differences were observed in diversity and composition between GDM and non-GDM groups in the M1 phase, we observed differential structures and composition in the M6 phase between the 2 groups (P < .05), with lower levels of diversity, 6 depleted and 10 enriched gut microbes among infants born to GDM mothers. The dynamic changes in alpha diversity from the M1 to M6 phase were also significantly different according to GDM status (P < .05). Moreover, we found that the altered gut bacteria in the GDM group were correlated with infants' growth. CONCLUSION: Maternal GDM was associated not only with the community structure and composition in the gut microbiota of offspring at a specific time point, but also with the differential changes from birth to infancy. Altered colonization of the GDM infants' gut microbiota might affect their growth. Our findings underscore the critical impact of GDM on the formation of early-life gut microbiota and on the growth and development of infants.