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SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/virologia , Imunidade Inata/genética , Pandemias , SARS-CoV-2/genéticaRESUMO
The controllable construction of complex metal-organic coordination polymers (CPs) merits untold scientific and technological potential, yet remains a grand challenge of one-step construction and modulating simultaneously valence states of metals and topological morphology. Here, a thiocyanuric acid (TCA)-triggered strategy is presented to one-step rapid synthesis a double-crystalline Prussian blue analogue hetero-superstructure (PBA-hs) that comprises a Co3[Fe(CN)6]2 cube overcoated with a KCo[Fe(CN)6] shell, followed by eight self-assembled small cubes on vertices. Unlike common directing surfactants, TCA not only acts as a trigger for the fast growth of KCo[Fe(CN)6] on the Co3[Fe(CN)6]2 phase resulting in a PBA-on-PBA hetero-superstructure, but also serves as a flange-like bridge between them. By combining experiments with simulations, a deprotonation-induced electron transfer (DIET) mechanism is proposed for formation of second phase in PBA-hs, differing from thermally and photo-induced electron transfer processes. To prove utility, the calcined PBA-hs exhibits enhanced oxygen evolution reaction performance. This work provides a new method to design of novel CPs for enriching chemistry and material science. This work offers a practical approach to design novel CPs for enriching chemistry and material science.
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PURPOSE: To compare the clinical characteristics, virus serotype, and outcome in cases of mild and severe enteroviral infection at a tertiary neonatal intensive care unit in China. METHODS: A retrospective analysis of cases hospitalized between June and August 2019. Samples (stool or throat swabs) were examined using reverse transcription polymerase chain reaction. Positive cases were divided into two groups: mild infection and severe infection. RESULTS: A total of 149 cases were assigned to one of two groups: mild infection (n = 104) and severe infection (n = 45). There were no significant differences between the groups in terms of sex, gestational age, birth weight, mode of delivery, and onset within 7 days. Clinical symptoms in both groups mostly resembled sepsis (fever, rash, poor feeding, and lethargy); however, there were significant variations in concomitant symptoms such as hepatitis, thrombocytopenia, encephalitis, coagulopathy, and myocarditis. Severe cases were more likely to have abnormal complete blood counts, biochemical parameters, and cerebrospinal fluid markers. The predominant serotypes implicated in neonatal enterovirus infections were echoviruses and Coxsackievirus B. Invasive ventilation, intravenous immunoglobulin, vasoactive medications, and blood product transfusions were often required, with high mortality rates among severe cases. CONCLUSION: We found significant differences between mild and severe cases of neonatal enterovirus infection with respect to complications, laboratory findings, and enterovirus serotypes. It is crucial to exercise caution when newborns exhibit symptoms of sepsis, during an enterovirus outbreak. Anemia, thrombocytopenia, abnormal liver function, and coagulation dysfunction should be monitored closely as they could indicate the presence of a severe enteroviral infection.
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Infecções por Enterovirus , Centros de Atenção Terciária , Humanos , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/virologia , Estudos Retrospectivos , Recém-Nascido , Masculino , Feminino , China/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Estudos de Casos e Controles , Enterovirus/isolamento & purificação , Enterovirus/classificação , Enterovirus/genética , Unidades de Terapia Intensiva Neonatal , Índice de Gravidade de Doença , Sorogrupo , População do Leste AsiáticoRESUMO
Pediatric otolaryngology surgeries are crucial interventions requiring careful consideration of surgical methods to optimize outcomes. The choice between open and minimally invasive surgical approaches in this context warrants thorough investigation. While both methods aim to address ear, nose, and throat conditions in children, a comparative study assessing their impact on crucial factors such as intraoperative parameters, wound healing, complications, and postoperative pain is essential. This study aims to compare the effects of open and minimally invasive surgical methods on wound healing and infection in pediatric otolaryngology surgery, and provide a scientific basis for the selection of surgical methods. Two groups of patients were selected, with 90 people in each group. One group received open surgery and the other received minimally invasive surgery. Recording the intraoperative time, anesthesia time, and intraoperative blood loss; the number of days required for wound healing; the occurrence of wound-related complications; the comparison of pain on postoperative Days 1, 3, and 7; and the factors influencing postoperative wound healing were analyzed. In the minimally invasive surgery group, the intraoperative time was shorter, the anesthesia time was relatively reduced, and the amount of bleeding was significantly reduced. Wounds also take fewer days to heal and have lower rates of wound-related complications. When comparing the pain on 1, 3, and 7 days after surgery, the minimally invasive surgery group had relatively mild pain. Analysis of postoperative wound healing factors showed that minimally invasive surgical methods have a positive impact on healing. In pediatric otolaryngology surgery, minimally invasive surgery performs better than open surgery in terms of intraoperative operation time, anesthesia time, blood loss, wound healing time, complication rate, and postoperative pain. Therefore, minimally invasive surgery may be a safer and more effective surgical method.
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Otolaringologia , Faringe , Criança , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos , Dor Pós-Operatória , CicatrizaçãoRESUMO
The hollow sandwich core-shell micro-nanomaterials are widely used in materials, chemistry, and medicine, but their fabrication, particularly for transition metal phosphides (TMPs), remains a great challenge. Herein, a general synthesis strategy is presented for binary TMPs hollow sandwich heterostructures with vertically interconnected nanosheets on the inside and outside surfaces of polyhedron FeCoPx /C, demonstrated by a variety of transition metals (including Co, Fe, Cd, Mn, Cu, Cr, and Ni). Density functional theory (DFT) calculation reveals the process and universal mechanism of layered double hydroxide (LDH) growth on Prussian blue analog (PBA) surface in detail for the first time, which provides the theoretical foundations for feasibility and rationality of the synthesis strategy. This unique structure exhibits a vertical nanosheet-shell-vertical nanosheet configuration combining the advantages of sandwich, hollow and vertical heterostructures, effectively achieving their synergistic effect. As a proof-of-concept of their applications, the CoNiPx @FeCoPx /C@CoNiPx hollow sandwich polyhedron architectures (representative samples) show excellent catalytic performance for the oxygen evolution reaction (OER) in alkaline electrolytes. This work provides a general method for constructing hollow-sandwich micro-nanostructures, which provides more ideas and directions for design of micro-nano materials with special geometric topology.
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Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions to improve predictive utility and constructed a deep-learning-based pipeline recognizing normal vs. abnormal kidney tissue compartments and mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides of transplant biopsies (60 training and 33 testing) were used to quantify pathological lesions specific for interstitium, tubules and mononuclear leukocyte infiltration. The pipeline was applied to the whole slide images from 789 transplant biopsies (478 baseline [pre-implantation] and 311 post-transplant 12-month protocol biopsies) in two independent cohorts (GoCAR: 404 patients, AUSCAD: 212 patients) of transplant recipients to correlate composite lesion features with graft loss. Our model accurately recognized kidney tissue compartments and mononuclear leukocytes. The digital features significantly correlated with revised Banff 2007 scores but were more sensitive to subtle pathological changes below the thresholds in the Banff scores. The Interstitial and Tubular Abnormality Score (ITAS) in baseline samples was highly predictive of one-year graft loss, while a Composite Damage Score in 12-month post-transplant protocol biopsies predicted later graft loss. ITASs and Composite Damage Scores outperformed Banff scores or clinical predictors with superior graft loss prediction accuracy. High/intermediate risk groups stratified by ITASs or Composite Damage Scores also demonstrated significantly higher incidence of estimated glomerular filtration rate decline and subsequent graft damage. Thus, our deep-learning approach accurately detected and quantified pathological lesions from baseline or post-transplant biopsies and demonstrated superior ability for prediction of post-transplant graft loss with potential application as a prevention, risk stratification or monitoring tool.
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Aprendizado Profundo , Transplante de Rim , Biópsia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Rim/patologia , Transplante de Rim/efeitos adversosRESUMO
OBJECTIVE: Long noncoding RNA nuclear enriched abundant transcript 1 (lnc-NEAT1) and its target microRNA-125a (miR-125a) are reported to regulate immune and inflammation process in allergic rhinitis (AR). Hence, this study intended to investigate the correlation between lnc-NEAT1 and miR-125a expressions, as well as their clinical values in pediatric AR patients. METHODS: Peripheral blood mononuclear cell samples from 80 pediatric AR patients, 40 disease controls (DCs), and 40 healthy controls (HCs) were collected to detect lnc-NEAT1 and miR-125a expressions by reverse transcription-quantitative polymerase chain reaction. For pediatric AR patients only, serum interferon-gamma (IFN-γ) and interleukin (IL)-10 were measured by enzyme linked immunosorbent assay; meanwhile, T helper (Th) 1 and Th2 cells in CD4+ T cells were analyzed by flow cytometry. RESULTS: Lnc-NEAT1 was overexpressed, while miR-125a downregulated in pediatric AR patients compared to DCs and HCs (all p < 0.001). Moreover, lnc-NEAT1 expression negatively correlated with miR-125a expression in pediatric AR patients (p = 0.002), but not in DCs (p = 0.226) or HCs (p = 0.237). Furthermore, in pediatric AR patients, lnc-NEAT1 expression positively associated with TNSS (p < 0.001), sneezing score (p = 0.006), and congestion score (p = 0.008); miR-125a expression was negatively related to TNSS (p < 0.001), itching score (p = 0.040), and sneezing score (p = 0.005). Additionally, lnc-NEAT1 expression positively, while miR-125a expression negatively correlated with Th2 cells and IL-10 (all p < 0.05), but they were not correlated with Th1 cells or IFN-γ in pediatric AR patients. CONCLUSION: Circulating lnc-NEAT1 and miR-125a are aberrantly expressed and linked with Th2 cells and symptom severity in pediatric allergic rhinitis.
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MicroRNAs , RNA Longo não Codificante , Rinite Alérgica , Criança , Humanos , Leucócitos Mononucleares , MicroRNAs/genética , RNA Longo não Codificante/genética , Rinite Alérgica/genética , Células Th2RESUMO
Piezoelectric actuators with a flexible displacement amplification structure are widely used in the fields of precision driving and positioning. The displacement curve of conventional piezoelectric actuators is asymmetrical and non-linear, which leads to large non-linear errors and reduced positioning accuracy of these piezoelectric actuators. In this paper, a bidirectional active drive piezoelectric actuator is proposed, which suppresses the hysteresis phenomenon to a certain extent and reduces the non-linear error. Based on the deformation theory of the beam, a theoretical model of the rhombus mechanism was established, and the key parameters affecting the drive performance were analyzed. Then, the static and dynamic characteristics of series piezoelectric actuators were analyzed by the finite element method. A prototype was manufactured and the output performance was tested. The results show that the actuator can achieve a bidirectional symmetric output of amplification displacement, with a maximum value of 91.45 µm and a resolution of 35 nm. In addition, compared with the hysteresis loop of the piezoelectric stack, the nonlinear error is reduced by 62.94%.
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A recently synthesized novel molecule (named CAT-1) exhibits intriguing near-infrared (NIR) thermally activated delayed fluorescence (TADF) close to 1000 nm wavelength; however, the mechanism behind these intrinsic properties is not fully understood. Herein, we unravel that the fluorescence emission spectrum with a broad wavelength range (770-950 nm) of CAT-1 is primarily induced by hydrogen bond steric hindrance based on density functional theory and Marcus theory. It is found that the hydrogen bond steric hindrance plays a critical role in inhibiting the twist of the configuration of different excited states, which leads to the minor driving force for fast electron trapping between the excited states, as well as small internal reorganization energy caused by less changed geometric configuration. Furthermore, such steric hindrance will cause a more distorted plane, resulting in a less favorable electron delocalization. A faster reverse intersystem crossing (RISC) rate is then obtained due to the nearly unchanged conformation between excited states caused by steric hindrance, although the spin-orbit coupling is small. Consequently, the NIR TADF with a longer wavelength can be emitted in CAT-1. This work shows that the hydrogen bond steric hindrance can fine-tune the electronic interactions of the donor and acceptor units to control the TADF.
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This study was intended to clarify the potential of applying the long-chain noncoding RNA H19/miR-29a axis in keloid treatment by elucidating its correlation with the activity of fibroblasts. In this study, 80 keloid tissues, 63 normal fibrous tissues, and 91 normal skin tissues were collected in advance, and concurrently, fibroblasts separated from the tissues were cultured. Besides this, the si-H19, pcDNA3.1-H19, miR-29a mimic, and miR-29a inhibitor were transfected to keloid fibroblasts, whose proliferation, apoptosis, and metastasis were appraised by employing the colony formation assay, flow cytometry, and transwell assay. In addition, the luciferase reporter gene assay was carried out to determine whether targeted regulation was present between H19 and miR-29a, as well as between miR-29a and COL1A1. The study results demonstrated that keloid tissues and fibroblasts exhibited observably upregulated H19 expression and downregulated miR-29a expression, relative to normal skin tissues and fibroblasts (P < .05). Also observed was a negative correlation between H19 expression and miR-29a expression among the gathered keloid tissues (rs = -.267, P = .017). Furthermore, in vitro transfection of pcDNA3.1-H19 or miR-29a inhibitor could intensify viability, proliferation, migration, and invasion of the fibroblasts (P < .05), while silencing of H19 and overexpression of miR-29a hindered both metastasis and multiplication of the fibroblasts significantly (P < .05). In addition, H19 was capable of altering miR-29a expression within fibroblasts by directly sponging it, and overexpression of COL1A1 could deter the impact of miR-29a on viability, proliferation, migration, and invasion of fibroblasts (P < .05). In conclusion, H19 might facilitate proliferation and metastasis of fibroblasts by modifying downstream miR-29a and COL1A1, which was expected to allow for development of keloid-targeted treatments.
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Colágeno Tipo I/metabolismo , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica , Queloide/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Movimento Celular , Proliferação de Células , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Transição Epitelial-Mesenquimal , Fibroblastos/metabolismo , Humanos , Queloide/genética , Queloide/metabolismo , MicroRNAs/genética , Prognóstico , Transdução de SinaisRESUMO
Donor-recipient (D-R) differences at human leukocyte antigen (HLA) loci are currently incorporated into organ sharing, allocation and immunosuppression decisions. However, while acute rejection episodes have substantially diminished, progressive histologic damage occurs in allografts and improved long-term survival remains an unrealized goal among kidney recipients. Here we tested the hypothesis that non-HLA dependent, genome-wide D-R genetic differences could contribute to unchecked alloimmunity with histologic and functional consequences, culminating in long-term allograft failure. Genome-wide single nucleotide polymorphism (SNP) array data, excluding the HLA region, was utilized from 385 transplants to study the role of D-R differences upon serial histology and allograft survival. ADMIXTURE analysis was performed to quantitatively estimate ancestry in each D-R pair and PLINK was used to estimate the proportion of genome-shared identity-by-descent (pIBD) between D-R pairs. Subsequently, quantitative measures of recipient ancestry based on non-HLA SNPs was associated with death-censored allograft survival in adjusted Cox models. In D-R pairs of similar ancestry, pIBD was significantly associated with allograft survival independent of HLA mismatches in 224 transplants. Surprisingly, pIBD and recipient ancestry were not associated with clinical or subclinical rejection at any time post-transplant. Significantly, in multivariable analysis, pIBD inversely correlated with vascular intimal fibrosis in 160 biopsies obtained less than one year which in turn was significantly associated with allograft survival. Thus, our novel data show that non-HLA D-R differences associate with early vascular intimal fibrosis and allograft survival.
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Transplante de Rim , Aloenxertos , Fibrose , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/genética , Antígenos HLA/genética , Humanos , Rim , Transplante de Rim/efeitos adversosRESUMO
The energetic alignment of band edges at the interface plays a central role in determining the properties and applications of two-dimensional (2D) van der Waals (vdW) heterostructures. Generally, three conventional heterojunction types (type-I, type-II, and type-III) have widely been investigated and used in diverse fields. Unconventional band alignments (type-IV, type-V, and type-VI) are, however, hitherto unreported in the vdW heterostructures. We find that 2D binary semiconductors composed of group IV-V elements manifest a similar electronic structure, offering in principle the possibility of designing heterostructures with novel band alignments due to the hybridization of band-edge states. We first show here that a 2D SiAs/GeP heterostructure exhibits a type-VI band alignment, which is induced by the interlayer pz orbital hybridization, and a transition of band alignment from type-VI to type-V occurs when strain or electric field is applied over a critical value. The unconventional band alignments and their transition natures enable broad application of these vdW heterostructures in special opto-electronic devices and energy conversion.
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BACKGROUND: In kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies. METHODS: We examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort. RESULTS: Study participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss. CONCLUSIONS: Our targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients.
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Perfilação da Expressão Gênica , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Idoso , Biomarcadores/metabolismo , Biópsia , Feminino , Genômica , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Inflamação , Estimativa de Kaplan-Meier , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Prospectivos , Fatores de Risco , Análise de Sequência de RNARESUMO
With the rapid development of the internet of things, radio frequency identification (RFID) technology plays an important role in various fields. However, RFID systems are vulnerable to cloning attacks. This is the fabrication of one or more replicas of a genuine tag, which behave exactly as a genuine tag and fool the reader to gain legal authorization, leading to potential financial loss or reputation damage. Many advanced solutions have been proposed to combat cloning attacks, but they require extra hardware resources, or they cannot detect a clone tag in time. In this article, we make a fresh attempt to counterattack tag cloning based on spatiotemporal collisions. We propose adaptable clone detection (ACD), which can intuitively and accurately display the positions of abnormal tags in real time. It uses commercial off-the-shelf (COTS) RFID devices without extra hardware resources. We evaluate its performance in practice, and the results confirm its success at detecting cloning attacks. The average accuracy can reach 98.7%, and the recall rate can reach 96%. Extensive experiments show that it can adapt to a variety of RFID application scenarios.
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A high light-absorption coefficient and long-range hot-carrier transport of hybrid organic-inorganic perovskites give huge potential to their composites in solar energy conversion and environmental protection. Understanding interfacial interactions and their effects are paramount for designing perovskite-based heterostructures with desirable properties. Herein, we systematically investigated the interfacial interactions in monolayer and few-layer SnS/CH3 NH3 PbI3 heterostructures and their effects on the electronic and optical properties of these structures by density functional theory. It was found that the interfacial interactions in SnS/CH3 NH3 PbI3 heterostructures were van der Waals (vdW) interactions, and they were found to be insensitive to the layer number of 2D SnS sheets. Interestingly, although their band gap decreased upon increasing the layer number of SnS, the near-gap electronic states and optical absorption spectra of these heterostructures were found to be strikingly similar. This feature was determined to be critical for the design of 2D layered SnS-based heterostructures. Strong absorption in the ultraviolet and visible-light regions, typeâ II staggered band alignment at the interface, and few-layer SnS as an active co-catalyst make 2D SnS/CH3 NH3 PbI3 heterostructures promising candidates for photocatalysis, photodetectors, and solar energy harvesting and conversion. These results provide first insight into the nature of interfacial interactions and are useful for designing hybrid organic-inorganic perovskite-based devices with novel properties.
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Elimination of pollutants from water is one of the greatest challenges in resolving global environmental issues. Herein, we report a high-surface-area mesoporous g-C3N4 nanosheet with remarkable high adsorption capacity and photocatalytic performance, which is prepared through directly polycondensation of urea followed by a consecutive one-step thermal exfoliation strategy. This one-pot method to prepare mesoporous g-C3N4 nanosheet is facile and rapid in comparison with others. The superior adsorption capacity of the fabricated mesoporous g-C3N4 nanostructures is demonstrated by a model organic pollutant-methylene blue (MB), which is up to 72.2 mg/g, about 6 times as that of the largest value of various g-C3N4 adsorbents reported so far. Moreover, this kind of porous g-C3N4 nanosheet exhibits high photocatalytic activity to MB and phenol degradation. Particularly, the regenerated samples show excellent performance of pollutant removal after consecutive adsorption/degradation cycles. Therefore, this mesoporous g-C3N4 nanosheet may be an attractive robust metal-free material with great promise for organic pollutant elimination.
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Understanding the interfacial interaction is of paramount importance for rationally designing carbon nanomaterial-based hybrids with optimal performance for electronics, optoelectronics, sensing, advanced energy conversion and storage. Here, we firstly reveal that both covalent and noncovalent interactions simultaneously exist in carbon nanotube (CNT)/Ag3PO4 hybrids by studying systematically the electronic and optical properties to elucidate the mechanism of their enhanced photocatalytic performance. Metallic CNT(9,0) may chemically or physically interact with the Ag3PO4(100) surface depending on its relative orientations, whereas semiconducting CNT(10,0) can only noncovalently functionalize Ag3PO4. The C-Ag bond in the covalently bonded hybrid and type-II, staggered, band alignment in noncovalent hybrids lead to a robust separation of photoexcited charge carriers between two constituents, thus enhancing the photocatalytic activity. The small band gap makes the CNT/Ag3PO4 hybrids absorb sunlight from the ultraviolet to infrared region. Moreover, CNTs are not only effective sensitizers, but also highly active co-catalysts in hybrids. The results can be rationalized by the available experiments, thereby partly resolving a debate on the interpretation of the experimental results, and paving the way for developing highly efficient carbon-based nanophotocatalysts.
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The goal of this study was to determine how B-cell-activating factor of the TNF family (BAFF) availability influences selection of the autoreactive B-cell repertoire in NZB/W and NZW/BXSB lupus-prone mice bearing the site-directed heavy-chain transgene 3H9 that encodes for anti-dsDNA and anti-cardiolipin (CL) autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild-type cells and could be identified by green fluorescent protein. The light-chain repertoire associated with the 3H9 heavy chain in naive and antigen-activated B-cell subsets was assessed using single-cell polymerase chain reaction. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability, and there were only modest and physiologically non-relevant effects on the naive B-cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9-encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain, BAFF inhibition did not alter the selection of 3H9-encoded B cells in the germinal center, but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B-cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans.
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Large yellow croaker (Larimichthys crocea) is one of the most valuable marine fish in southern China. Given to the rapid development of aquaculture industry, the L. crocea was subjected to ciliate ectoparasite Cryptocaryon irritans. It therefore is indispensable and urgent to understand the mechanism of L. crocea host defense against C. irritans infection. In the present study, the extensively analysis at the transcriptome level for Cryptocaryoniasis in L. crocea was carried out. These results showed that 15,826,911, 16,462,921, and 15,625,433 paired-end clean reads were obtained from three cDNA libraries (A: 0 theronts/fish, B: 12,000 theronts/fish, and C: 24,000 theronts/fish) of the L. crocea immune-related tissues by Illumina paired-end sequencing technology. Totally, 30,509 unique transcript fragments (unigenes) were assembled, with an average length of 1715 bp. In B/A, C/A, and C/B pairwise comparison, 972, 900, and 1126 genes showed differential expression respectively. Differently expressed immune-related genes (DEIGs) were scrutinized, in B/A pairwise comparison, 48 genes showed differential expression, including 26 up-regulated genes and 22 down-regulated genes in B; in C/A pairwise comparison, there were 39 DEIGs, including 7 up-regulated genes and 32 down-regulated genes in C; in C/B pairwise comparison, 40 genes showed differential expression, including 11 up-regulated genes and 29 down-regulated genes in C. There were 16 DEIGs enriched KEGG pathways, in which the complement and coagulation cascades pathway was the top most DEIGs enriched pathway (B:A = 42; C:A = 28; C:B = 42). The coagulation and fibrinolytic system was in a highly active state after infected by C. irritans with non-lethal concentration; the alternative complement pathway may play an important role in the early stages of C. irritans infection. These results demonstrated that low-concentration infection can significantly induce the immunological response in fishes, however, when fishes were in fatal conditions, the immunity was suppressed.
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Infecções por Cilióforos/veterinária , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Imunidade Inata , Perciformes , Transcriptoma , Animais , Cilióforos/fisiologia , Infecções por Cilióforos/genética , Infecções por Cilióforos/imunologia , Infecções por Cilióforos/parasitologia , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Doenças dos Peixes/imunologia , Doenças dos Peixes/parasitologia , Proteínas de Peixes/metabolismo , Análise de Sequência de RNA/veterináriaRESUMO
Recent experiments have shown that the photocatalytic activity of g-C3N4 can be greatly enhanced by C60 modification, however, a fundamental understanding of its mechanistic operation is still lacking. Using first-principles calculations, the interfacial effects of C60/g-C3N4 nanocomposites on the electronic properties, charge transfer and optical response have been explored in detail. For different stacking patterns, the two constituents are always linked by van der Waals (vdW) forces without any exception, and form type-II heterojunctions in most cases. The valence band maximum and conduction band minimum of these heterostructures are dominated by the unsaturated nitrogen (N2) atoms and C60 molecule, respectively, which strongly interact with each other, resulting in strong charge transfer between the two involved constituents and an obvious bending of the g-C3N4 sheets. The unsaturated N2 atoms included in the interfaces have a significant influence on promoting the photocatalytic performance, while the existence of saturated nitrogen (N1 and N3) atoms lying in the interfaces will weaken the interfacial interactions between C60 molecules and the g-C3N4 monolayers. Moreover, the sensitive optical response and satisfactory type-II band alignment clearly show that the C60/g-C3N4 heterostructure is an outstanding photocatalyst for hydrogen production. We proposed a deep insight (the role of nitrogen) into understanding the improved photocatalytic ability of the C60/g-C3N4 nanocomposites, which may contribute to the rational design of both C60/g-C3N4 and g-C3N4-based nanocomposite photocatalysts.