Short-distance vesicle transport via phase separation.

In addition to long-distance molecular motor-mediated transport, cellular vesicles also need to be moved at short distances with defined directions to meet functional needs in subcellular compartments but with unknown mechanisms. Such short-distance vesicle transport does not involve molecular motors. Here, we demonstrate, using synaptic vesicle (SV) transport as a paradigm, that phase separation of synaptic proteins with vesicles can facilitate regulated, directional vesicle transport between different presynaptic bouton sub-compartments. Specifically, a large coiled-coil scaffold protein Piccolo, in response to Ca2+ and via its C2A domain-mediated Ca2+ sensing, can extract SVs from the synapsin-clustered reserve pool condensate and deposit the extracted SVs onto the surface of the active zone protein condensate. We further show that the Trk-fused gene, TFG, also participates in COPII vesicle trafficking from ER to the ER-Golgi intermediate compartment via phase separation. Thus, phase separation may play a general role in short-distance, directional vesicle transport in cells.

The MGF300-2R protein of African swine fever virus is associated with viral pathogenicity by promoting the autophagic degradation of IKKα and IKKß through the recruitment of TOLLIP.

The multigene family genes (MGFs) in the left variable region (LVR) of the African swine fever virus (ASFV) genome have been reported to be involved in viral replication in primary porcine alveolar macrophages (PAMs) and virulence in pigs. However, the exact functions of key MGFs in the LVR that regulate the replication and virulence of ASFV remain unclear. In this study, we identified the MGF300-2R gene to be critical for viral replication in PAMs by deleting different sets of MGFs in the LVR from the highly virulent strain ASFV HLJ/18 (ASFV-WT). The ASFV mutant lacking the MGF300-2R gene (Del2R) showed a 1-log reduction in viral titer, and induced higher IL-1ß and TNF-α production in PAMs than did ASFV-WT. Mechanistically, the MGF300-2R protein was found to interact with and degrade IKKα and IKKß via the selective autophagy pathway. Furthermore, we showed that MGF300-2R promoted the K27-linked polyubiquitination of IKKα and IKKß, which subsequently served as a recognition signal for the cargo receptor TOLLIP-mediated selective autophagic degradation. Importantly, Del2R exhibited a significant reduction in both replication and virulence compared with ASFV-WT in pigs, likely due to the increased IL-1ß and TNF-α, indicating that MGF300-2R is a virulence determinant. These findings reveal that MGF300-2R suppresses host innate immune responses by mediating the degradation of IKKα and IKKß, which provides clues to paving the way for the rational design of live attenuated vaccines to control ASF.

A p21-ATD mouse model for monitoring and eliminating senescent cells and its application in liver regeneration post injury.

Cellular senescence associates with pathological aging and tissue dysfunctions. Studies utilizing mouse models for cell lineage tracings have emphasized the importance of senescence heterogeneity in different organs and cell types. Here, we constructed a p21- (Akaluc - tdTomato - Diphtheria Toxin Receptor [DTR]) (ATD) mouse model to specifically study the undefined mechanism for p21-expressing senescent cells in the aged and liver injury animals. The successful expressions of these genes enabled in vitro flow cytometric sorting, in vivo tracing, and elimination of p21-expressing senescent cells. During the natural aging process, p21-expressing cells were found in various tissues of p21-ATD mice. Eliminating p21-expressing cells in the aged p21-ATD mice recovered their multiple biological functions. p21-ATD/Fah-/- mice, bred from p21-ATD mice and fumarylacetoacetate hydrolase (Fah)-/- mice of liver injury, showed that the majority of their senescent hepatocytes were the phenotype of p21+ rather than p16+. Furthermore, eliminating the p21-expressing hepatocytes significantly promoted the engraftment of grafted hepatocytes and facilitated liver repopulation, resulting in significant recovery from liver injury. Our p21-ATD mouse model serves as an optimal model for studying the pattern and function of p21-expressing senescent cells under the physical and pathological conditions during aging.

Transcriptome profiling in swine macrophages infected with African swine fever virus at single-cell resolution.

African swine fever virus (ASFV) is the causative agent of African swine fever, a highly contagious and usually fatal disease in pigs. The pathogenesis of ASFV infection has not been clearly elucidated. Here, we used single-cell RNA-sequencing technology to survey the transcriptomic landscape of ASFV-infected primary porcine alveolar macrophages. The temporal dynamic analysis of viral genes revealed increased expression of viral transmembrane genes. Molecular characteristics in the ASFV-exposed cells exhibited the activation of antiviral signaling pathways with increased expression levels of interferon-stimulated genes and inflammatory- and cytokine-related genes. By comparing infected cells with unexposed cells, we showed that the unfolded protein response (UPR) pathway was activated in low viral load cells, while the expression level of UPR-related genes in high viral load cells was less than that in unexposed cells. Cells infected with various viral loads showed signature transcriptomic changes at the median progression of infection. Within the infected cells, differential expression analysis and coregulated virus­host analysis both demonstrated that ASFV promoted metabolic pathways but inhibited interferon and UPR signaling, implying the regulation pathway of viral replication in host cells. Furthermore, our results revealed that the cell apoptosis pathway was activated upon ASFV infection. Mechanistically, the production of tumor necrosis factor alpha (TNF-α) induced by ASFV infection is necessary for cell apoptosis, highlighting the importance of TNF-α in ASFV pathogenesis. Collectively, the data provide insights into the comprehensive host responses and complex virus­host interactions during ASFV infection, which may instruct future research on antiviral strategies.

The mutations on the envelope glycoprotein D contribute to the enhanced neurotropism of the pseudorabies virus variant.

The pseudorabies virus (PRV) TJ strain, a variant of PRV, induces more severe neurological symptoms and higher mortality in piglets and mice than the PRV SC strain isolated in 1980. However, the mechanism underlying responsible for the discrepancy in virulence between these strains remains unclear. Our study investigated the differences in neurotropism between PRV TJ and PRV SC using both in vitro and in vivo models. We discovered that PRV TJ enters neural cells more efficiently than PRV SC. Furthermore, we found that PRV TJ has indistinguishable genomic DNA replication capability and axonal retrograde transport dynamics compared to the PRV SC. To gain deeper insights into the mechanisms underlying these differences, we constructed gene-interchanged chimeric virus constructs and assessed the affinity between envelope glycoprotein B, C, and D (gD) and corresponding receptors. Our findings confirmed that mutations in these envelope proteins, particularly gD, significantly contributed to the heightened attachment and penetration capabilities of PRV TJ. Our study revealed the critical importance of the gDΔR278/P279 and gDV338A in facilitating viral invasion. Furthermore, our observations indicated that mutations in envelope proteins have a more significant impact on viral invasion than on virulence in the mouse model. Our findings provide valuable insights into the roles of natural mutations on the PRV envelope glycoproteins in cell tropism, which sheds light on the relationship between cell tropism and clinical symptoms and offers clues about viral evolution.

Short-chain fatty acids ameliorate experimental anti-glomerular basement membrane disease.

BACKGROUND: Short-chain fatty acids (SCFAs), as the link between gut microbiota and the immune system, had been reported to be protective in many autoimmune diseases by the modulation of T cell differentiation. The pathogenic role of autoreactive Th1 and Th17 cells and the protective role of Treg cells in the pathogenesis of anti-GBM disease have been fully demonstrated. Thus, the present study aimed to investigate the therapeutic effects of SCFAs in a rat model of anti-GBM disease. MATERIALS AND METHODS: Experimental anti-GBM disease was constructed by immunizing Wistar Kyoto rats with a nephrogenic T cell epitope α3127-148, and intervened by sodium acetate, sodium propionate, or sodium butyrate, 150 mM in the drinking water from day 0 to 42. Kidney injury was accessed by the biochemical analyzer, immunofluorescence, and immunohistochemistry. Antibody response was detected by ELISA. T cell clustering and proliferation were detected by flow cytometry. Human kidney 2 (HK2) cells were stimulated in vitro and cytokines were assessed by quantitative real-time PCR. RESULTS: Treatment with sodium acetate, sodium propionate, or sodium butyrate ameliorated the severity of kidney impairment in rats with anti-GBM glomerulonephritis. In the sodium butyrate-treated rats, the urinary protein, serum creatinine, and blood urea nitrogen levels were significantly lower; the percentage of crescent formation in glomeruli was significantly reduced; and the kidneys showed reduced IgG deposition, complement activation, T cell, and macrophage infiltration as well as the level of circulating antibodies against anti-α3(IV)NC1. The treatment of sodium butyrate reduced the α3127-148-specific T cell activation and increased the Treg cells differentiation and the intestinal beneficial bacteria flora. It also alleviated the damage of HK2 cells treated with inflammatory factors and complement. CONCLUSION: Treatment with SCFAs, especially butyrate, alleviated anti-GBM nephritis in rat model, indicating its potential therapeutic effects in clinical usage.

All-Solid-State Mg-Air Battery Enhanced with Free-Standing N-Doped 3D Nanoporous Graphene.

Nitrogen (N) doping of graphene with a three-dimensional (3D) porous structure, high flexibility, and low cost exhibits potential for developing metal-air batteries to power electric/electronic devices. The optimization of N-doping into graphene and the design of interconnected and monolithic graphene-based 3D porous structures are crucial for mass/ion diffusion and the final oxygen reduction reaction (ORR)/battery performance. Aqueous-type and all-solid-state primary Mg-air batteries using N-doped nanoporous graphene as air cathodes are assembled. N-doped nanoporous graphene with 50-150 nm pores and ≈99% porosity is found to exhibit a Pt-comparable ORR performance, along with satisfactory durability in both neutral and alkaline media. Remarkably, the all-solid-state battery exhibits a peak power density of 72.1 mW cm-2 ; this value is higher than that of a battery using Pt/carbon cathodes (54.3 mW cm-2 ) owing to the enhanced catalytic activity induced by N-doping and rapid air breathing in the 3D porous structure. Additionally, the all-solid-state battery demonstrates better performances than the aqueous-type battery owing to slow corrosion of the Mg anode by solid electrolytes. This study sheds light on the design of free-standing and catalytically active 3D nanoporous graphene that enhances the performance of both Mg-air batteries and various carbon-neutral-technologies using neutral electrolytes.

Confinement Effect and 3D Design Endow Unsaturated Single Ni Atoms with Ultrahigh Stability and Selectivity toward CO2 Electroreduction.

Developing single-atomic catalysts with superior selectivity and outstanding stability for CO2 electroreduction is desperately required but still challenging. Herein, confinement strategy and three-dimensional (3D) nanoporous structure design strategy are combined to construct unsaturated single Ni sites (Ni-N3) stabilized by pyridinic N-rich interconnected carbon nanosheets. The confinement agent chitosan and its strong interaction with g-C3N4 nanosheet are effective for dispersing Ni and restraining their agglomeration during pyrolysis, resulting in ultrastable Ni single-atom catalyst. Due to the confinement effect and structure advantage, such designed catalyst exhibits a nearly 100% selectivity and remarkable stability for CO2 electroreduction to CO, exceeding most reported state-of-the-art catalysts. Specifically, the CO Faradaic efficiency (FECO) maintains above 90% over a broad potential range (-0.55 to -0.95 V vs. RHE) and reaches a maximum value of 99.6% at a relatively low potential of -0.67 V. More importantly, the FECO is kept above 95% within a long-term 100 h electrolyzing. Density functional theory (DFT) calculations explain the high selectivity for CO generation is due to the high energy barrier required for hydrogen evolution on the unsaturated Ni-N3. This work provides a new designing strategy for the construction of ultrastable and highly selective single-atom catalysts for efficient CO2 conversion.

The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

The D129L protein of African swine fever virus interferes with the binding of transcriptional coactivator p300 and IRF3 to prevent beta interferon induction.

IMPORTANCE: African swine fever (ASF) is an acute, hemorrhagic, and severe porcine infectious disease caused by African swine fever virus (ASFV). ASF outbreaks severely threaten the global pig industries and result in serious economic losses. No safe and efficacious commercial vaccine is currently available except in Vietnam. To date, large gaps in the knowledge concerning viral biological characteristics and immunoevasion strategies have hindered the ASF vaccine design. In this study, we demonstrate that pD129L negatively regulates the type I interferon (IFN) signaling pathway by interfering with the interaction of the transcriptional coactivator p300 and IRF3, thereby inhibiting the induction of type I IFNs. This study reveals a novel immunoevasion strategy employed by ASFV, shedding new light on the intricate mechanisms for ASFV to evade the host immune responses.

Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.

Development and application of an indirect ELISA for detection of antibodies against emerging atypical porcine pestivirus.

BACKGROUND: Atypical porcine pestivirus (APPV) is a newly discovered swine pestivirus, which can cause congenital tremor and high mortality in newborn piglets and subclinical infection in adult pigs, leading to significant impacts on the pig industry. Currently, there is no approved serological method to assess APPV infection status in pig farms. METHODS: In this study, the envelope glycoprotein E2 of APPV was highly expressed in suspension HEK293 cells, and further an indirect enzyme-linked immunosorbent assay based on the recombinant E2 protein (E2-iELISA) was developed and evaluated. RESULTS: The reaction parameters of the E2-iELISA were optimized, and the cutoff value was determined to be 0.2 by analyzing S/P values of 165 negative sera against APPV that were confirmed by virus neutralization test (VNT). Specificity test showed that the method had no cross-reaction with other common swine viruses. The E2-iELISA was evaluated using a panel of swine sera, and showed high sensitivity (113/120, 94.2%) and specificity (65/70, 92.9%), and the agreement rate with VNT was 93.7% (178/190). Subsequently, the E2-iELISA was utilized to investigate the seroprevalence of APPV in pig herds of China. When detecting 1368 pig serum samples collected from nine provinces in China, the overall seroprevalence of APPV was 73.9% (1011/1368). CONCLUSION: Our findings suggest that the E2-iELISA is specific and sensitive, and could be a valuable tool for serological surveillance of APPV infection in pigs.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden.

BACKGROUND: The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. OBJECTIVE: We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. STUDY DESIGN: A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. RESULTS: The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. CONCLUSION: The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

A Millimeter-Wave Broadband Multi-Mode Substrate-Integrated Gap Waveguide Traveling-Wave Antenna with Orbit Angular Momentum.

Orbit angular momentum (OAM) has been considered a new dimension for improving channel capacity in recent years. In this paper, a millimeter-wave broadband multi-mode waveguide traveling-wave antenna with OAM is proposed by innovatively utilizing the transmitted electromagnetic waves (EMWs) characteristic of substrate-integrated gap waveguides (SIGWs) to introduce phase delay, resulting in coupling to the radiate units with a phase jump. Nine "L"-shaped slot radiate elements are cut in a circular order at a certain angle on the SIGW to generate spin angular momentum (SAM) and OAM. To generate more OAM modes and match the antenna, four "Π"-shaped slot radiate units with a 90° relationship to each other are designed in this circular array. The simulation results show that the antenna operates at 28 GHz, with a -10 dB fractional bandwidth (FBW) = 35.7%, ranging from 25.50 to 35.85 GHz and a VSWR ≤ 1.5 dB from 28.60 to 32.0 GHz and 28.60 to 32.0 GHz. The antenna radiates a linear polarization (LP) mode with a gain of 9.3 dBi at 34.0~37.2 GHz, a l = 2 SAM-OAM (i.e., circular polarization OAM (CP-OAM)) mode with 8.04 dBi at 25.90~28.08 GHz, a l = 1 and l = 2 hybrid OAM mode with 5.7 dBi at 28.08~29.67 GHz, a SAM (i.e., left/right hand circular polarization (L/RHCP) mode with 4.6 dBi at 29.67~30.41 GHz, and a LP mode at 30.41~35.85 GHz. In addition, the waveguide transmits energy with a bandwidth ranging from 26.10 to 38.46 GHz. Within the in-band, only a quasi-TEM mode is transmitted with an energy transmission loss |S21| ≤ 2 dB.

Self-Floating Nanoporous High-Entropy Oxides with Tunable Bandgap for Efficient Solar Seawater Desalination.

Nanoporous high-entropy oxide (np-HEO) powders with tunable composition are integrated with a poly(vinylidene fluoride) network to create self-floating solar absorber films for seawater desalination. By progressively increasing the element count, we obtain an optimized 9-component AlNiCoFeCrMoVCuTi-Ox. Density functional theory (DFT) calculations reveal a remarkable reduction in its bandgap, facilitating the light-induced migration of electrons to conduction bands to generate electron-hole pairs, which recombine to produce heat. Simultaneously, the intricate light reflection and refraction pathways, shaped by the nanoporous structure, coupled with the reduced thermal conductivity attributed to the suboptimal crystalline quality of the np-HEO ensure an effective conversion of captured light into thermal energy. Consequently, all these films demonstrate an impressive absorbance rate exceeding 93% across the 250-2500 nm spectral range. Under one sun, the surface temperature of the 9-component film rapidly rises to 110 °C within 90 s with a high pure water evaporation rate of 2.16 kg m-2 h-1.

Highly Thermally Conductive Aramid Nanofiber Composite Films with Synchronous Visible/Infrared Camouflages and Information Encryption.

The development of highly thermally conductive composites that combine visible light/infrared camouflage and information encryption has been endowed with great significance in facilitating the application of 5G communication technology in military fields. This work uses aramid nanofibers (ANF) as the matrix, hetero-structured silver nanowires@boron nitride nanosheets (AgNWs@BNNS) prepared by in situ growth as fillers, which are combined to fabricate sandwich structured thermally conductive and electrically insulating (BNNS/ANF)-(AgNWs@BNNS)-(BNNS/ANF) (denoted as BAB) composite films by "filtration self-assembly, air spraying, and hot-pressing" method. When the mass ratio of AgNWs@BNNS to BNNS is 1 : 1 and the total mass fraction is 50 wt %, BAB composite film has the maximum in-plane thermal conductivity coefficient (λ∥ of 10.36 W/(m ⋅ K)), excellent electrical insulation (breakdown strength and volume resistivity of 41.5 kV/mm and 1.21×1015â€…Ω â‹… cm, respectively) and mechanical properties (tensile strength of 170.9 MPa). 50 wt % BAB composite film could efficiently reduce the equilibrium temperature of the central processing unit (CPU) working at full power, resulting in 7.0 °C lower than that of the CPU solely integrated with ANF directly. In addition, BAB composite film boasts adaptive visible light/infrared dual camouflage properties on cement roads and jungle environments, as well as the function of fast encryption of QR code information within 24 seconds.

Mapping the T cell epitopes of the M-type transmembrane phospholipase A2 receptor in primary membranous nephropathy.

The M-type phospholipase A2 receptor (PLA2R) is the major autoantigen of primary membranous nephropathy (MN). Despite many studies on B-cell epitopes recognized by antibodies, little is known about T-cell epitopes. Herein, we synthesized 123 linear peptides, each consisting of 15-22 amino acids with 8-12 amino acid overlaps, across ten domains of PLA2R. Their binding capacity to risk (DRB1∗1501, DRB1∗0301) and protective (DRB1∗0901, DRB1∗0701) HLA molecules was then assessed by flow cytometry. Proliferation of CD4+ T cells from patients with anti-PLA2R positive MN was analyzed after peptide stimulation. Cytokines produced by activated peripheral blood mononuclear cells were measured by cytometric bead arrays. We identified 17 PLA2R peptides that bound to both DRB1∗1501 and DRB1∗0301 molecules with high capacity. Some of these peptides showed decreased binding to heterozygous DRB1∗1501/0901 and DRB1∗0301/0701. Ten of the 17 peptides (CysR1, CysR10, CysR12, FnII-3, CTLD3-9, CTLD3-10, CTLD3-11, CTLD5-2-1, CTLD7-1 and CTLD7-2) induced significant proliferation of CD4+ T cells from patients with MN than cells from healthy individuals. Upon activation by these peptides, peripheral blood mononuclear cells from patients with MN produced higher levels of pro-inflammatory cytokines, predominantly IL-6, TNF-α, IL-10, IL-9 and IL-17. Thus, we mapped and identified ten peptides in the CysR, FnII, CTLD3, CTLD5, and CTLD7 domains of PLA2R as potential T-cell epitopes of MN. These findings are a first step towards developing peptide-specific immunotherapies.

Knockdown of LINC01087 inhibits gastric cancer malignant behavior by regulating the miR-135a-5p/CAAP1 axis.

Long noncoding RNAs play important roles in the occurrence and development of many malignant cancers. This study focuses on the effects of LINC01087 on gastric cancer and its underlying mechanism. In the present study, LINC01087 and CAAP1 were found to be upregulated, and miR-135a-5p was diminished in gastric cancer specimens and cells. Inhibition of LINC01087 resulted in cell proliferation inhibition and induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-3 and caspase-9. An investigation of the signaling pathway revealed that the effects on proliferation and apoptosis following LINC01087 knockdown were mediated by suppression of CAAP1. Furthermore, application of a miR-135a-5p inhibitor or overexpression of CAAP1 could attenuate the apoptotic effect achieved by LINC01087 inhibition, confirming the involvement of miR-135a-5p/CAAP1 signaling in the occurrence of gastric cancer. In conclusion, the LINC01087/miR-135a-5p/CAAP1 axis modulates gastric cancer tumorigenesis and pathogenesis and presents new insight into gastric cancer targeted therapy.

Denoising brain networks using a fixed mathematical phase change in independent component analysis of magnitude-only fMRI data.

Brain networks extracted by independent component analysis (ICA) from magnitude-only fMRI data are usually denoised using various amplitude-based thresholds. By contrast, spatial source phase (SSP) or the phase information of ICA brain networks extracted from complex-valued fMRI data, has provided a simple yet effective way to perform the denoising using a fixed phase change. In this work, we extend the approach to magnitude-only fMRI data to avoid testing various amplitude thresholds for denoising magnitude maps extracted by ICA, as most studies do not save the complex-valued data. The main idea is to generate a mathematical SSP map for a magnitude map using a mapping framework, and the mapping framework is built using complex-valued fMRI data with a known SSP map. Here we leverage the fact that the phase map derived from phase fMRI data has similar phase information to the SSP map. After verifying the use of the magnitude data of complex-valued fMRI, this framework is generalized to work with magnitude-only data, allowing use of our approach even without the availability of the corresponding phase fMRI datasets. We test the proposed method using both simulated and experimental fMRI data including complex-valued data from University of New Mexico and magnitude-only data from Human Connectome Project. The results provide evidence that the mathematical SSP denoising with a fixed phase change is effective for denoising spatial maps from magnitude-only fMRI data in terms of retaining more BOLD-related activity and fewer unwanted voxels, compared with amplitude-based thresholding. The proposed method provides a unified and efficient SSP approach to denoise ICA brain networks in fMRI data.

Revealing Atomic Configuration and Synergistic Interaction of Single-Atom-Based Zn-Co-Fe Trimetallic Sites for Enhancing Oxygen Reduction and Evolution Reactions.

Anchoring single metal atom to carbon supports represents an exceptionally effective strategy to maximize the efficiency of catalysts. Recently, dual-atom catalysts (DACs) emerge as an intriguing candidate for atomic catalysts, which perform better than single-atom catalysts (SACs). However, the clarification of the polynary single-atom structures and their beneficial effects remains a daunting challenge. Here, atomically dispersed triple Zn-Co-Fe sites anchored to nitrogen-doped carbon (ZnCoFe-N-C) prepared by one-step pyrolysis of a designed metal-organic framework precursor are reported. The atomically isolated trimetallic configuration in ZnCoFe-N-C is identified by annular dark-field scanning transmission electron microscopy and spectroscopic techniques. Benefiting from the synergistic effect of trimetallic single atoms, nitrogen, and carbon, ZnCoFe-N-C exhibits excellent catalytic performance in bifunctional oxygen reduction/evolution reactions in an alkaline medium, outperforming other SACs and DACs. The ZnCoFe-N-C-based Zn-air battery exhibits a high specific capacity (liquid state: 931.8 Wh kgZn -1 ), power density (liquid state: 137.8 mW cm-2 ; all-solid-state: 107.9 mW cm-2 ), and good cycling stability. Furthermore, density-functional theory calculations rationalize the excellent performance by demonstrating that the ZnCoFe-N-C catalyst has upshifted d-band center that enhances the adsorption of the reaction intermediates.