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BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.
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Circuncisão Masculina , Infecções por HIV , Homossexualidade Masculina , Humanos , Masculino , Adulto , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , China/epidemiologia , Incidência , Comportamento Sexual , Análise de Intenção de TratamentoRESUMO
Lithium metal anodes are an appealing choice for rechargeable batteries due to their exceptionally high theoretical capacity of about 3860 mA h g-1. However, the uneven plating/stripping of lithium metal anodes leads to serious dendrite growth and low coulombic efficiency, curtailing their practical applications. The 3D scaffold/host strategy emerges as a promising approach that concurrently mitigates volume changes and dendrite growth. This review provides an overview of the regulating mechanisms behind scaffold/host materials for dendrite-free applications, tracing their historical development and recent progress across five key stages: material texture selection, lithiophilic modification, structural design, multi-strategy integration, and practical implementation. Additionally, scaffold/host materials are categorized based on their material texture, with a thorough examination of their respective advantages and drawbacks. Furthermore, this tutorial outlines the obstacles and complexities associated with implementing scaffold/host strategies. Finally, the determining factors that affect the electrochemical performances of scaffold/host materials are discussed, along with possible design criteria and future development prospects. This tutorial aims to provide guidance for researchers on the design of advanced scaffold/host materials for advanced Li metal anodes for batteries.
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BACKGROUND: Diabetes mellitus (DM)-induced testicular damage is associated with sexual dysfunction and male infertility in DM patients. However, the pathogenesis of DM-induced testicular damage remains largely undefined. METHODS: A streptozotocin (STZ)-induced diabetic model and high glucose (HG)-treated in vitro diabetic model were established. The histological changes of testes were assessed by H&E staining. Serum testosterone, iron, MDA and GSH levels were detected using commercial kits. Cell viability and lipid peroxidation was monitored by MTT assay and BODIPY 581/591 C11 staining, respectively. qRT-PCR, immunohistochemistry (IHC) or Western blotting were employed to detect the levels of BRD7, Clusterin, EZH2 and AMPK signaling molecules. The associations among BRD7, EZH2 and DNMT3a were detected by co-IP, and the transcriptional regulation of Clusterin was monitored by methylation-specific PCR (MSP) and ChIP assay. RESULTS: Ferroptosis was associated with DM-induced testicular damage in STZ mice and HG-treated GC-1spg cells, and this was accompanied with the upregulation of BRD7. Knockdown of BRD7 suppressed HG-induced ferroptosis, as well as HG-induced Clusterin promoter methylation and HG-inactivated AMPK signaling in GC-1spg cells. Mechanistical studies revealed that BRD7 directly bound to EZH2 and regulated Clusterin promoter methylation via recruiting DNMT3a. Knockdown of Clusterin or inactivation of AMPK signaling reverses BRD7 silencing-suppressed ferroptosis in GC-1spg cells. In vivo findings showed that lack of BRD7 protected against diabetes-induced testicular damage and ferroptosis via increasing Clusterin expression and activating AMPK signaling. CONCLUSION: BRD7 suppressed Clusterin expression via modulating Clusterin promoter hypermethylation in an EZH2 dependent manner, thereby suppressing AMPK signaling to facilitate ferroptosis and induce diabetes-associated testicular damage.
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Proteínas Quinases Ativadas por AMP , Clusterina , Metilação de DNA , Diabetes Mellitus Experimental , Ferroptose , Regiões Promotoras Genéticas , Transdução de Sinais , Testículo , Animais , Masculino , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Clusterina/genética , Clusterina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/complicações , DNA Metiltransferase 3A/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Ferroptose/genética , Camundongos Endogâmicos C57BL , Testículo/metabolismo , Testículo/patologiaRESUMO
Manganese dioxide (MnO2) is an attractive cathode material for aqueous zinc batteries (AZBs) owing to its environmental benignity, low cost, high operating voltage, and high theoretical capacity. However, the severe dissolution of Mn2+ leads to rapid capacity decay. Herein, a self-assembled layer of amino-propyl phosphonic acid (AEPA) on the MnO2 surface, which significantly improves its cycle performance is successfully modified. Specifically, AEPA can be firmly attached to MnO2 through a strong chemical bond, forming a hydrophobic, and uniform organic coating layer with a few nanometers thickness. This coating layer can significantly inhibit the dissolution of Mn2+ by avoiding the direct contact between the electrolyte and cathode, thus enhancing the structural integrity and redox reversibility of MnO2. As a result, the MnO2@AEPA cathode achieves a high reversible capacity of 223 mAh g-1 at 0.5 A g-1 and a high capacity retention of 97% after 1700 cycles at 1 A g-1. This work provides new insights in developing stable Mn-based cathodes for aqueous batteries.
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Ameson portunus (Microsporidia) has caused serious economic losses to the aquaculture industry of swimming crab, Portunus trituberculatus. The hemolymph and hepatopancreas are the main immune organs of P. trituberculatus, and the main sites of A. portunus infection. Elucidating the response characteristics of hemolymph and hepatopancreas to microsporidian infection facilitates the development of microsporidiosis prevention and control strategy. This study performed comparative transcriptomic analysis of hemolymph (PTX/PTXA) and hepatopancreas (PTG/PTGA) of P. trituberculatus uninfected and infected with A. portunus. The results showed that there were 223 and 1309 differentially expressed genes (DEGs) in PTX/PTXA and PTG/PTGA, respectively. The lysosome pathway was significantly enriched after the invasion of the hemolymph by A. portunus. Also, immune-related genes were all significantly up-regulated in the hemolymph and hepatopancreas, suggesting that the invasion by A. portunus may activate host immune responses. Unlike hemolymph, antioxidant and detoxification-related genes were also significantly up-regulated in the hepatopancreas. Moreover, metabolism-related genes were significantly down-regulated in the hepatopancreas, suggesting that energy synthesis, resistance to pathogens, and regulation of oxidative stress were suppressed in the hepatopancreas. Hemolymph and hepatopancreas have similarity and tissue specificity to microsporidian infection. The differential genes and pathways identified in this study can provide references for the prevention and control of microsporidiosis.
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Braquiúros , Microsporídios , Microsporidiose , Animais , Braquiúros/genética , Hemolinfa , Hepatopâncreas/metabolismo , Microsporídios/genética , Microsporidiose/metabolismo , TranscriptomaRESUMO
A visible-light-induced decarboxylative cascade reaction of acryloylbenzamides with alkyl N-hydroxyphthalimide (NHP) esters for the synthesis of various 4-alkyl isoquinolinediones mediated by triphenylphosphine (PPh3) and sodium iodide (NaI) was developed. This operationally simple protocol proceeded via the photoactivation of electron donor-acceptor (EDA) complexes between N-hydroxyphthalimide esters and NaI/PPh3, resulting in multiple carbon-carbon bond formations without the use of precious metal complexes or synthetically elaborate organic dyes, which provided an alternative practical approach to synthesize diverse isoquinoline-1,3(2H,4H)-dione derivatives.
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BACKGROUND: This study aimed to compare low Hartmann's procedure (LHP) with abdominoperineal resection (APR) for rectal cancer (RC) regarding postoperative complications. METHOD: RC patients receiving radical LHP or APR from 2015 to 2019 in our center were retrospectively enrolled. Patients' demographic and surgical information was collected and analyzed. Propensity score matching (PSM) was used to balance the baseline information. The primary outcome was the incidence of major complications. All the statistical analysis was performed by SPSS 22.0 and R. RESULTS: 342 individuals were primarily included and 134 remained after PSM with a 1:2 ratio (50 in LHP and 84 in APR). Patients in the LHP group were associated with higher tumor height (P < 0.001). No significant difference was observed between the two groups for the incidence of major complications (6.0% vs. 1.2%, P = 0.290), and severe pelvic abscess (2% vs. 0%, P = 0.373). However, the occurrence rate of minor complications was significantly higher in the LHP group (52% vs. 21.4%, P < 0.001), and the difference mainly lay in abdominal wound infection (10% vs. 0%, P = 0.006) and bowel obstruction (16% vs. 4.8%, P = 0.028). LHP was not the independent risk factor of pelvic abscess in the multivariate analysis. CONCLUSION: Our data demonstrated a comparable incidence of major complications between LHP and APR. LHP was still a reliable alternative in selected RC patients when primary anastomosis was not recommended.
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Complicações Pós-Operatórias , Protectomia , Pontuação de Propensão , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Protectomia/métodos , Protectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Colostomia/métodos , Colostomia/efeitos adversos , IncidênciaRESUMO
BACKGROUND: Prostate cancer is one of the most common malignant tumors in middle-aged and elderly men and carries significant prognostic implications, and recent studies suggest that dual-energy computed tomography (DECT) utilizing new virtual monoenergetic images can enhance cancer detection rates. This study aimed to assess the impact of virtual monoenergetic images reconstructed from DECT arterial phase scans on the image quality of prostate lesions and their diagnostic performance for prostate cancer. METHODS: We conducted a retrospective analysis of 83 patients with prostate cancer or prostatic hyperplasia who underwent DECT scans at Meizhou People's Hospital between July 2019 and December 2023. The variables analyzed included age, tumor diameter and serum prostate-specific antigen (PSA) levels, among others. We also compared CT values, signal-to-noise ratio (SNR), subjective image quality ratings, and contrast-to-noise ratio (CNR) between virtual monoenergetic images (40-100 keV) and conventional linear blending images. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic efficacy of virtual monoenergetic images (40 keV and 50 keV) compared to conventional images. RESULTS: Virtual monoenergetic images at 40 keV showed significantly higher CT values (168.19 ± 57.14) compared to conventional linear blending images (66.66 ± 15.5) for prostate cancer (P < 0.001). The 50 keV images also demonstrated elevated CT values (121.73 ± 39.21) compared to conventional images (P < 0.001). CNR values for the 40 keV (3.81 ± 2.13) and 50 keV (2.95 ± 1.50) groups were significantly higher than the conventional blending group (P < 0.001). Subjective evaluations indicated markedly better image quality scores for 40 keV (median score of 5) and 50 keV (median score of 5) images compared to conventional images (P < 0.05). ROC curve analysis revealed superior diagnostic accuracy for 40 keV (AUC: 0.910) and 50 keV (AUC: 0.910) images based on CT values compared to conventional images (AUC: 0.849). CONCLUSIONS: Virtual monoenergetic images reconstructed at 40 keV and 50 keV from DECT arterial phase scans substantially enhance the image quality of prostate lesions and improve diagnostic efficacy for prostate cancer.
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Neoplasias da Próstata , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Curva ROC , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Hiperplasia Prostática/diagnóstico por imagem , Idoso de 80 Anos ou mais , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Antígeno Prostático Específico/sangueRESUMO
Ameson portunus, the recently discovered causative agent of "toothpaste disease" of pond-cultured swimming crabs in China has caused enormous economic losses in aquaculture. Understanding the process of spore germination is helpful to elucidate the molecular mechanism of its invasion of host cells. Here, we obtained mature and germinating spores by isolation and purification and in vitro stimulation, respectively. Then, non-germinated and germinated spores were subjected to the comparative transcriptomic analysis to disclose differential molecular responses of these two stages. The highest germination rate, i.e., 71.45 %, was achieved in 0.01 mol/L KOH germination solution. There were 9,609 significantly differentially expressed genes (DEGs), with 685 up-regulated and 8,924 down-regulated DEGs. The up-regulated genes were significantly enriched in ribosome pathway, and the down-regulated genes were significantly enriched in various metabolic pathways, including carbohydrate metabolism, amino acid metabolism and other metabolism. The results suggested that spores require various carbohydrates and amino acids as energy to support their life activities during germination and synthesize large amounts of ribosomal proteins to provide sites for DNA replication, transcription, translation and protein synthesis of the spores of A. portunus within the host cells. Functional genes related to spore germination, such as protein phosphatase CheZ and aquaporin, were also analyzed. The analysis of transcriptome data and identification of functional genes will help to understand the process of spore germination and invasion.
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Microsporídios , Transcriptoma , Animais , Esporos , Microsporídios/genética , Perfilação da Expressão Gênica , Esporos Bacterianos/genéticaRESUMO
Flexible electronic devices have shown increasingly promising value facilitating our daily lives. However, flexible spintronic devices remain in their infancy. Here, this research demonstrates a type of nonvolatile, low power dissipation, and programmable flexible spin logic device, which is based on the spin-orbit torque in polyimide (PI)/Ta/Pt/Co/Pt heterostructures fabricated via capillary-assisted electrochemical delamination. The magnetization switching ratio is shown to be about 50% for the flexible device and does not change after 100 cycles of bending, indicating the device has stable performance. By designing the path of pulse current, five Boolean logic gates AND, NAND, NOT, NOR, and OR can be realized in an integrated two-element device. Moreover, such peeling-off devices can be successfully transferred to almost any substrate, such as paper and human skin, and maintain high performance. The flexible PI/Ta/Pt/Co/Pt spin logic device serves as logic-in-memory architecture and can be used in wearable electronics.
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More than 70% of tumor patients require radiotherapy. Medical electron linear accelerators are important high-end radiotherapy equipment for tumor radiotherapy. With the application of artificial intelligence technology in medical electron linear accelerator, radiotherapy has evolved from ordinary radiotherapy to today's intelligent radiotherapy. This study introduces the development history, working principles and system composition of medical electron linear accelerators. It outlines the key technologies for improving the performance of medical linear electron accelerators, including beam control, multi-leaf collimator, guiding technology and dose evaluation. It also looks forward to the development trend of major radiotherapy technologies, such as biological guided radiotherapy, FLASH radiotherapy and intelligent radiotherapy, which provides references for the development of medical electron linear accelerators.
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Elétrons , Neoplasias , Humanos , Inteligência Artificial , Aceleradores de Partículas , Dosagem RadioterapêuticaRESUMO
BACKGROUND: The present study aimed to identify the module genes and key gene functions and biological pathways of septic shock (SS) through integrated bioinformatics analysis. METHODS: In the study, we performed batch correction and principal component analysis on 282 SS samples and 79 normal control samples in three datasets, GSE26440, GSE95233 and GSE57065, to obtain a combined corrected gene expression matrix containing 21,654 transcripts. Patients with SS were then divided into three molecular subtypes according to sample subtyping analysis. RESULTS: By analyzing the demographic characteristics of the different subtypes, we found no statistically significant differences in gender ratio and age composition among the three groups. Then, three subtypes of differentially expressed genes (DEGs) and specific upregulated DEGs (SDEGs) were identified by differential gene expression analysis. We found 7361 DEGs in the type I group, 5594 DEGs in the type II group, and 7159 DEGs in the type III group. There were 1698 SDEGs in the type I group, 2443 in the type II group, and 1831 in the type III group. In addition, we analyzed the correlation between the expression data of 5972 SDEGs in the three subtypes and the gender and age of 227 patients, constructed a weighted gene co-expression network, and identified 11 gene modules, among which the module with the highest correlation with gender ratio was MEgrey. The modules with the highest correlation with age composition were MEgrey60 and MElightyellow. Then, by analyzing the differences in module genes among different subgroups of SS, we obtained the differential expression of 11 module genes in four groups: type I, type II, type III and the control group. Finally, we analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of all module DEGs, and the GO function and KEGG pathway enrichment of different module genes were different. CONCLUSIONS: Our findings aim to identify the specific genes and intrinsic molecular functional pathways of SS subtypes, as well as further explore the genetic and molecular pathophysiological mechanisms of SS.
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Mapas de Interação de Proteínas , Choque Séptico , Humanos , Mapas de Interação de Proteínas/genética , Choque Séptico/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Biomarcadores , Biologia ComputacionalRESUMO
Te-based materials with excellent electrical conductivity and ultra-high volume specific capacity have attracted much attention for the cost-efficient aqueous Zn batteries. However, the construction of functional structures with mild volume expansion and suppressed shuttle effects, enabling an expanded lifespan, is still a challenge for conversion-type materials. Herein, the carbon-coated zinc telluride nanowires (ZnTe@C NWs) are rationally designed as a high-performance cathode material for aqueous Zn batteries. The carbon-coated1D nanostructure could not only provide optimized transmission path for electrons and ions, but also help to maintain structure integrity upon volume variation and suppress intermediates dissolution, endowing the ZnTe@C NWs with improved cycling stability and reaction kinetics. Consequently, a reversible six-electron reaction mechanism of ZnTe@C NWs based on Te2- /Te4+ conversion with excellent output capacity (586 mAh g-1 at 0.1 A g-1 ) and lifespan (>250 mAh g-1 retained for 400 cycles at 1 A g-1 ) is eventually achieved.
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Organic resistive switching memory (ORSM) shows great potential for neotype memory devices due to the preponderances of simple architecture, low power consumption, high switching speed and feasibility of large-area fabrication. Herein, solution-processed ternary ORSM devices doped with bipolar materials were achieved with high ON/OFF ratio and outstanding device stability. The resistive switching performance was effectively ameliorated by doping two bipolar materials (DpAn-InAc and DpAn-5BzAc) in different blending concentration into the PVK:OXD-7 donor-accepter system. Compared with the binary system (PVK: 30 wt% OXD-7), the ON/OFF ratios of the ternary devices doped with 6 wt% DpAn-5BzAc were greatly increased from 7.91 × 102to 4.98 × 104, with the operating voltage (â£Vset-Vresetâ£) declined from 4.90 V to 2.25 V, respectively. Additionally, the stability of resistance state and uniformity of operating voltage were also significantly optimized for the ternary devices. For comparison, ternary devices doped with DpAn-InAc have been explored, which also achieved improved resistive switching behavior. A detailed analysis of electrical characteristics and the internal charge transfer properties of ORSM was performed to unveil the performance enhancement in ternary devices. Results indicate that the use of bipolar materials favors the efficient operation of OSRMs with proper energy level alignment and effective charge transfer.
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BACKGROUND: The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. METHODS: In China's Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration-time curve across 24 h at a steady state (ssAUC0-24) of 50-100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. RESULTS: This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan-Meier's 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0-24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. CONCLUSION: A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.
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Injúria Renal Aguda , Sepse , Humanos , Polimixina B/farmacologia , Polimixina B/uso terapêutico , Monitoramento de Medicamentos , Sepse/tratamento farmacológico , CarbapenêmicosRESUMO
Cadmium (Cd) and chromium (Cr) are widespread contaminants with a high risk to the environment and humans. Herein we isolated a novel strain of Serratia marcescens, namely strain S27, from soil co-contaminated with Cd and Cr. This strain showed strong resistance to Cd as well as Cr. S27 cells demonstrated Cd adsorption rate of 45.8% and Cr reduction capacity of 84.4% under optimal growth conditions (i.e., 30 °C, 200 rpm, and pH 7.5). Microscopic characterization of S27 cells revealed the importance of the functional groups C-O-C, C-H-O, C-C, C-H, and -OH, and also indicated that Cr reduction occurred on bacterial cell membrane. Cd(II) and Cr(VI) bioaccumulation on S27 cell surface was mainly in the form of Cd(OH)2 and Cr2O3, respectively. Further, metabolomic analyses revealed that N-arachidonoyl-l-alanine was the key metabolite that promoted Cd and Cr complexation by S27; it primarily promotes γ-linolenic acid (GLA) metabolism, producing siderophores and coordinating with organic acids to enhance metal bioavailability. To summarize, our results suggest that S27 is promising for the bioremediation of environments contaminated with Cd and Cr in tropical regions.
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Cádmio , Cromo , Humanos , Cromo/metabolismo , Serratia marcescens/metabolismo , Biodegradação Ambiental , AdsorçãoRESUMO
Cytosine arabinoside (Ara-C) is one of the most widely used chemotherapeutic agents for hematological malignancies. The residues of Ara-C have been detected in wastewater and river water with increased usage and discharge. As the ability to cross the placenta and the teratogenicity at low ng/L levels, the toxic effects on pregnant women and infants have been concerned. The toxicity of Ara-C exposure on early embryonic neurodevelopment has not been fully elucidated. In this study, pregnant C57BL/6 mice were injected with different doses of Ara-C on Gestation day (GD) 7.5 and assessed on GD11.5 and GD13.5 to explore the neural developmental effects of Ara-C. HE staining, immunofluorescence, western blot, EdU assay, and flow cytometry were utilized to determine the toxic effects of Ara-C in vivo and in vitro. Our results showed that Ara-C (15-22.5 mg/kg body weight) induced the occurrence of neural tube defects (NTDs). The expression of PH3 was markedly reduced in embryos with Ara-C-induced NTDs, compared to the control group (P < 0.05). In contrast, cell apoptosis was markedly increased. Increased expression levels of GFAP and decreased Nestin were observed in the embryonic brain tissues in Ara-C induced NTDs. The level of ß-catenin was also decreased on both GD11.5 and GD13.5. These results were confirmed in vitro using mouse Sv129 embryonic stem cells (mESC). Ara-C at a dose comparable to the environment level (0.05 nM) had cytotoxicity. Impaired Wnt/ß-catenin signaling pathway is involved in Ara-C exposure induced imbalance between cell proliferation, apoptosis, and differentiation, which might contribute to Ara-C-induced occurrence of NTDs. Our data indicated the environmental concentration of Ara-C had cytotoxicity and that maternal exposure to Ara-C induced NTDs. These results might provide more information to understand the environmental toxic impact of Ara-C on neurodevelopment.
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Our laboratory has identified and developed a unique human-engineered domain (HED) structure that was obtained from the human Alpha-2-macroglobulin receptor-associated protein based on the three-dimensional structure of the Z-domain derived from Staphylococcal protein A. This HED retains µM binding activity to the human IgG1CH2-CH3 elbow region. We determined the crystal structure of HED in association with IgG1's Fc. This demonstrated that HED preserves the same three-bundle helix structure and Fc-interacting residues as the Z domain. HED was fused to the single chain variable fragment (scFv) of mAb 4D5 to produce an antibody-like protein capable of interacting with the p185Her2/neu ectodomain and the Fc of IgG. When further fused with murine IFN-γ (mIFN-γ) at the carboxy terminus, the novel species exhibited antitumor efficacy in vivo in a mouse model of human breast cancer. The HED is a novel platform for the therapeutic utilization of engineered proteins to alleviate human disease.
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Neoplasias da Mama , Anticorpos de Cadeia Única , Humanos , Animais , Camundongos , Feminino , Anticorpos de Cadeia Única/genética , Proteína Estafilocócica A/químicaRESUMO
Arsenic contamination in a mining area is a potential threat to the local population. In the context of one-health, biological pollution in contaminated soil should be known and understandable. This study was conducted to clarify the effects of amendments on arsenic species and potential threat factors (e.g., arsenic-related genes (AMGs), antibiotic resistance genes (ARGs) and heavy-metal resistance genes (MRGs)). Ten groups (control (CK), T1, T2, T3, T4, T5, T6, T7, T8, and T9) were set up by adding different ratio of organic fertilizer, biochar, hydroxyapatite and plant ash. The maize crop was grown in each treatment. Compared with CK, the bioavailability of arsenic was reduced by 16.2%-71.8% in the rhizosphere soil treatments, and 22.4%-69.2% in the bulk soil treatments, except for T8. The component 2 (C2), component 3 (C3) and component 5 (C5) of dissolved organic matter (DOM) increased by 22.6%-72.6%, 16.8%-38.1%, 18.4%-37.1%, respectively, relative to CK in rhizosphere soil. A total of 17 AMGs, 713 AGRs and 492 MRGs were detected in remediated soil. The humidification of DOM might directly correlate with MRGs in both soils, while it was influenced directly on ARGs in bulk soil. This may be caused by the rhizosphere effect, which affects the interaction between microbial functional genes and DOM. These findings provide a theoretical basis for regulating soil ecosystem function from the perspective of arsenic contaminated soil.
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Arsênio , Poluentes do Solo , Matéria Orgânica Dissolvida , Rizosfera , Ecossistema , Solo , Poluentes do Solo/análiseRESUMO
Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase â £(COXâ £), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.