SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8+ T cells.

Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7-CD45RA+ effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.

Micropeptide CIP2A-BP encoded by LINC00665 inhibits triple-negative breast cancer progression.

TGF-ß signaling pathway plays a key role in breast cancer metastasis. Recent studies suggest that TGF-ß regulates tumor progression and invasion not only via transcriptional regulation, but also via translational regulation. Using both bioinformatics and experimental tools, we identified a micropeptide CIP2A-BP encoded by LINC00665, whose translation was downregulated by TGF-ß in breast cancer cell lines. Using TNBC cell lines, we showed that TGF-ß-activated Smad signaling pathway induced the expression of translation inhibitory protein 4E-BP1, which inhibited eukaryote translation initiation factor elF4E, leading to reduced translation of CIP2A-BP from LINC00665. CIP2A-BP directly binds tumor oncogene CIP2A to replace PP2A's B56γ subunit, thus releasing PP2A activity, which inhibits PI3K/AKT/NFκB pathway, resulting in decreased expression levels of MMP-2, MMP-9, and Snail. Downregulation of CIP2A-BP in TNBC patients was significantly associated with metastasis and poor overall survival. In the MMTV-PyMT model, either introducing CIP2A-BP gene or direct injection of CIP2A-BP micropeptide significantly reduced lung metastases and improved overall survival. In conclusion, we provide evidence that CIP2A-BP is both a prognostic marker and a novel therapeutic target for TNBC.

In Situ Biosynthesis of FeS Nanoparticles Boosts Current Generation in Bioelectrochemical Systems Through Efficient Electron Transfer.

The utility of electrochemical active biofilm in bioelectrochemical systems has received considerable attention for harvesting energy and chemical products. However, the slow electron transfer between biofilms and electrodes hinders the enhancement of performance and still remains challenging. Here, using Fe3O4 /L-Cys nanoparticles as precursors to induce biomineralization, a facile strategy for the construction of an effective electron transfer pathway through biofilm and biological/inorganic interface is proposed, and the underlying mechanisms are elucidated. Taking advantage of an on-chip interdigitated microelectrode array (IDA), the conductive current of biofilm that is related to the electron transfer process within biofilm is characterized, and a 2.10-fold increase in current output is detected. The modification of Fe3O4/L-Cys on the electrode surface facilitates the electron transfer between the biofilm and the electrode, as the bio/inorganic interface electron transfer resistance is only 16% compared to the control. The in-situ biosynthetic Fe-containing nanoparticles (e.g., FeS) enhance the transmembrane EET and the EET within biofilm, and the peak conductivity increases 3.4-fold compared to the control. The in-situ biosynthesis method upregulates the genes involved in energy metabolism and electron transfer from the transcriptome analysis. This study enriches the insights of biosynthetic nanoparticles on electron transfer process, holding promise in bioenergy conversion.

Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation.

Germline-encoded pattern recognition receptors (PRRs) recognize molecules frequently found in pathogens (pathogen-associated molecular patterns [PAMPs]) during viral infection. This process induces production of IFNs, leading to expression of IFN-stimulated genes to establish a cellular antiviral state against viral infection. However, aberrant activation of the IFN system may cause immunopathological damage and systemic autoimmune diseases such as systemic lupus erythematosus. Stringent control of IFN signaling activation is critical for maintaining homoeostasis of the immune system; yet, the mechanisms responsible for its precise regulation remain to be elucidated. In this study, we identified that ring finger protein 215 (RNF215), a zinc finger protein, was upregulated by viral infection in human macrophages. In addition, we demonstrated that RNF215 inhibited the production of type I IFNs at least in part via interacting with p65, a subunit of NF-κB, and repressed the accumulation of NF-κB in the promoter region of IFNB1. Moreover, we found that the expression of RNF215 negatively correlated with type I IFNs in patients with systemic lupus erythematosus, indicating that RNF215 plays an important role in the pathogenesis of autoimmune diseases. Collectively, our data identified RNF215 as a key negative regulator of type I IFNs and suggested RNF215 as a potential target for intervention in diseases with aberrant IFN production.

LncRNA MEG3 suppresses erastin-induced ferroptosis of chondrocytes via regulating miR-885-5p/SLC7A11 axis.

BACKGROUND: Ferroptosis is involved in osteoarthritis development; however, the roles of long noncoding RNAs (lncRNAs), including lncRNA MEG3, in the regulation of ferroptosis in osteoarthritis are still unclear. METHODS: In this study, qRT‒PCR and Western blotting assays were used to detect the expression of lncRNA MEG3, miR-885-5p, SLC7A11 and GPX4; MDA and CCK-8 assays were applied to analyse cellular MDA levels and cell viability, respectively. RESULT: Erastin elevated cellular MDA levels and decreased the viability of chondrocytes and the erastin-induced decline in cell viability was reversed by a ferroptosis inhibitor (ferrostatin-1). Erastin downregulated lncRNA MEG3, SLC7A11 and GPX4 and upregulated miR-885-5p. Silencing of lncRNA MEG3 increased miR-885-5p and downregulated SLC7A11 and GPX4 and further sensitized chondrocytes to erastin-induced ferroptosis. In contrast, overexpression of lncRNA MEG3 had opposite effects. Dual luciferase assays confirmed binding between lncRNA MEG3 and miR-885-5p and between miR-885-5p and the 3'UTR of SLC7A11. In the synovial fluids from patients with osteoarthritis compared with synovial fluids from normal controls, the RNA levels of lncRNA MEG3 and SLC7A11 were decreased and the miR-885-5p expression level was increased. CONCLUSION: Our findings indicated that lncRNA MEG3 overexpression alleviated ferroptosis in chondrocytes by affecting the miR-885-5p/SLC7A11 signalling pathway.

A universal and accurate LPMI method for calculating mismatch in heterogeneous ice nucleation.

The interfacial correlation factor f(m,x), where m refers to the interaction among ice, water and the substrate and x refers to the ratio of the critical nucleation size to the surface topography characteristic size of the substrate, plays a crucial role in the classical theory of heterogeneous ice nucleation as it significantly impacts the energy of nucleation. Generally, a smaller value of f(m,x) indicates a higher propensity for ice nucleation. The degree of structural compatibility between ice and the substrate greatly influences f(m,x), particularly on specific substrates. Several approaches have been proposed to calculate the lattice matching based on this idea, which allows whether a surface is favorable for nucleation to be determined. However, none of these methods adequately correlates the mismatch index with ice growth phenomena. In this paper, we embarked on a new attempt to calculate the mismatch index by combining the lattice parameter and Miller index (LPMI). Droplet freezing experiments have been carried out on α-Al2O3 and silicon surfaces with different Miller indices to verify the rationality of the LPMI method. Furthermore, we validated the LPMI method extensively against other works and further demonstrated its readiness, accuracy and universality for freezing problems. The results consistently show that δd = 2|di - ds|/(di + ds) with interplanar spacing more accurately predicts heterogeneous ice nucleation rates across a wide range of substrates than δ1 = (ai - as)/ai with the lattice parameter of ice and the substrate and is more generally applicable than δ2D = (di - di)/di with the distances between two adjacent and congener atoms on the same plane. We believe that the proposed approach will aid in the selection of substrates for promoting or inhibiting heterogeneous nucleation on a specific substrate.

Temperature-controlled microalgal biofilm detachment and harvesting assisted by ultrasonic from 3D porous substrates grafted with thermosensitive gels.

Microalgae have been renowned as the most promising energy organism with significant potential in carbon fixation. In the large-scale cultivation of microalgae, the 3D porous substrate with higher specific surface area is favorable to microalgae adsorption and biofilm formation, whereas difficult for biofilm detachment and microalgae harvesting. To solve this contradiction, N-isopropylacrylamide, a temperature-responsive gels material, was grafted onto the inner surface of the 3D porous substrate to form temperature-controllable interface wettability. The interfacial free energy between microalgae biofilm and the substrates increased from -63.02 mJ/m2 to -31.89 mJ/m2 when temperature was lowered from 32 °C to 17 °C, weakening the adsorption capacity of cells to the surface, and making the biofilm detachment ratio increased to 50.8%. When further cooling the environmental temperature to 4 °C, the detachment capability of microalgae biofilm kept growing. 91.6% of the cells in the biofilm were harvesting from the 3D porous substrate. And the biofilm detached rate was up to 19.84 g/m2/h, realizing the temperature-controlled microalgae biofilm harvesting. But, microalgae growth results in the secretion of extracellular polymeric substances (EPS), which enhanced biofilm adhesion and made cell detachment more difficult. Thus, ultrasonic vibration was used to reinforce biofilm detachment. With the help of ultrasonic vibration, microalgae biofilm detached rate increased by 143.45% to 41.07 g/m2/h. These findings provide a solid foundation for further development of microalgae biofilm detachment and harvesting technology.

Sirtuin 3 Mediated by Spinal cMyc-Enhancer of Zeste Homology 2 Pathway Plays an Important Role in Human Immunodeficiency Virus-Related Neuropathic Pain Model.

BACKGROUND: Clinical data demonstrate that chronic use of opioid analgesics increases neuropathic pain in people living with human immunodeficiency virus (HIV). Therefore, it is important to elucidate the molecular mechanisms of HIV-related chronic pain. In this study, we investigated the role of the transcription factor cMyc, epigenetic writer enhancer of zeste homology 2 (EZH2), and sirtuin 3 (Sirt3) pathway in HIV glycoprotein gp120 with morphine (gp120M)-induced neuropathic pain in rats. METHODS: Neuropathic pain was induced by intrathecal administration of recombinant gp120 with morphine. Mechanical withdrawal threshold was measured using von Frey filaments, and thermal latency using the hotplate test. Spinal expression of cMyc, EZH2, and Sirt3 were measured using Western blots. Antinociceptive effects of intrathecal administration of antisense oligodeoxynucleotide against cMyc, a selective inhibitor of EZH2, or recombinant Sirt3 were tested. RESULTS: In the spinal dorsal horn, gp120M upregulated expression of cMyc (ratio of gp120M versus control, 1.68 ± 0.08 vs 1.00 ± 0.14, P = .0132) and EZH2 (ratio of gp120M versus control, 1.76 ± 0.05 vs 1.00 ± 0.16, P = .006), and downregulated Sirt3 (ratio of control versus gp120M, 1.00 ± 0.13 vs 0.43 ± 0.10, P = .0069) compared to control. Treatment with intrathecal antisense oligodeoxynucleotide against cMyc, GSK126 (EZH2 selective inhibitor), or recombinant Sirt3 reduced mechanical allodynia and thermal hyperalgesia in this gp120M pain model. Knockdown of cMyc reduced spinal EZH2 expression in gp120M treated rats. Chromatin immunoprecipitation (ChIP) assay showed that enrichment of cMyc binding to the ezh2 gene promoter region was increased in the gp120M-treated rat spinal dorsal horn, and that intrathecal administration of antisense ODN against cMyc (AS-cMyc) reversed the increased enrichment of cMyc. Enrichment of trimethylation of histone 3 on lysine residue 27 (H3K27me3; an epigenetic mark associated with the downregulation of gene expression) binding to the sirt3 gene promoter region was upregulated in the gp120M-treated rat spinal dorsal horn; that intrathecal GSK126 reversed the increased enrichment of H3K27me3 in the sirt3 gene promoter. Luciferase reporter assay demonstrated that cMyc mediated ezh2 gene transcription at the ezh2 gene promoter region, and that H3K27me3 silenced sirt3 gene transcription at the gene promoter region. CONCLUSION: These results demonstrated that spinal Sirt3 decrease in gp120M-induced neuropathic pain was mediated by cMyc-EZH2/H3K27me3 activity in an epigenetic manner. This study provided new insight into the mechanisms of neuropathic pain in HIV patients with chronic opioids.

Racial Disparities in Medical Crowdfunding: The Role of Sharing Disparity and Humanizing Narratives.

Americans have increasingly turned to online crowdfunding to pay for healthcare costs, but our understanding of the inequalities in medical crowdfunding remains limited. This study investigates racial disparities in medical crowdfunding outcomes and examines the role of communication in amplifying, altering, or even reducing the disparities. Using data from 1,127 medical crowdfunding campaigns on GoFundMe, the study found that beneficiaries of color received significantly fewer donations than their White counterparts. The differences in donations between racial groups were partly attributable to sharing disparities. Campaigns for beneficiaries of color were shared less via e-mail or social media than campaigns for White beneficiaries. Campaign narratives with more humanizing details about beneficiaries were associated with more donations. However, humanizing details did not predict more shares, nor were they linked to smaller disparities in campaign outcomes between racial groups. Post-hoc analyses showed that more humanizing details were linked to fewer campaign donations for male beneficiaries of color. The findings contribute to the scholarship addressing the intersections of communication and health inequality on digital platforms.

Mitigating Identity Threat in Health Messaging: A Social Identity Complexity Perspective.

Health messages aiming to reduce red meat consumption may threaten multiple social identities because people's dietary choices are intertwined with personal, social, and cultural aspects of their lives. Leveraging social identity theory and the concept of social identity complexity, this experiment tested how identity-threatening messages affect people's intention to reduce red meat consumption and how the effect of identity threat may be moderated by messages highlighting the relationships between multiple identities that define a person. Participants (N = 409) read messages that varied identity threat (i.e. the extent to which people feel devalued because of their membership in a social group) and identity complexity (i.e. the extent to which people perceive multiple identities as independent). The study found that identity-threatening messages decreased intentions to reduce red meat consumption when people perceived their dietary identity as overlapping with other identities, but increased the intentions when the dietary identity was seen as independent from other identities. Further, the effects of identity threat and complexity were limited to people with high (vs. low) levels of red meat consumption. We discuss the role of identity complexity in alleviating identity threat and increasing persuasion.

Ancient Duplication and Lineage-Specific Transposition Determine Evolutionary Trajectory of ERF Subfamily across Angiosperms.

AP2/ERF transcription factor family plays an important role in plant development and stress responses. Previous studies have shed light on the evolutionary trajectory of the AP2 and DREB subfamilies. However, knowledge about the evolutionary history of the ERF subfamily in angiosperms still remains limited. In this study, we performed a comprehensive analysis of the ERF subfamily from 107 representative angiosperm species by combining phylogenomic and synteny network approaches. We observed that the expansion of the ERF subfamily was driven not only by whole-genome duplication (WGD) but also by tandem duplication (TD) and transposition duplication events. We also found multiple transposition events in Poaceae, Brassicaceae, Poales, Brassicales, and Commelinids. These events may have had notable impacts on copy number variation and subsequent functional divergence of the ERF subfamily. Moreover, we observed a number of ancient tandem duplications occurred in the ERF subfamily across angiosperms, e.g., in Subgroup IX, IXb originated from ancient tandem duplication events within IXa. These findings together provide novel insights into the evolution of this important transcription factor family.

Effects of miR-306 Perturbation on Life Parameters in the English Grain Aphid, Sitobion avenae (Homoptera: Aphididae).

MicroRNAs (miRNA) play a vital role in insects' growth and development and have significant potential value in pest control. Previously, we identified miR-306 from small RNA libraries within the English grain aphid, Sitobion avenae, a devasting insect pest for wheat. miR-306 not only involves in wing morphogenesis, but also is critically important for aphid survival. Its specific impacts on the life history traits, however, remain unclear. Here, we evaluate the impact of miR-306 perturbation on S. avenae populations using a two-sex life table approach. This comprehensive analysis revealed that miR-306 perturbation significantly prolongs the developmental stages (9.64% and 8.20%) and adult longevity of S. avenae, while decreasing pre-adult survival rate (41.45% and 38.74%) and slightly reducing average fecundity (5.80% and 13.05%). Overall, miR-306 perturbation negatively affects the life table parameters of the aphid population. The population prediction models show a significant decline in the aphid population 60 days post interference, compared to the control groups (98.14% and 97.76%). Our findings highlight the detrimental effects of miR-306 perturbation on S. avenae population growth and suggest potential candidate genes for the development of RNAi-based biopesticides targeted specifically at this pest species.

Light-Controlled Particle Enrichment Patterns in Droplets.

Precision manipulation of particle-enrichment patterns in droplets is challenging but important in biochemical analysis and clinical diagnosis. Herein, a light strategy for precisely manipulating particle enrichment patterns is reported. Focused laser irradiation to the droplet induces a Marangoni flow owing to a localized photothermal effect, which carries in-droplet particles and concentrates them at the laser-spot-acted region. Owing to high flexibility of light, multiple particle-enriched sites are formed in a droplet, and the concentrated particles can be transported and reconstructed on demand. In addition to the island-like enrichment pattern, this optical particle manipulation strategy enables the formation of various particle-enriched patterns, such as the line-shape and circle-shape patterns. Further, light directly acts on the working fluid instead of target particles, considerably weakening dependence on particle properties. For particles whose density is similar to that of the working fluid, a portion of particles can still be concentrated. It is also found that only a small portion of submicron particles can be concentrated, while nanoparticles are hardly concentrated by this light strategy. Moreover, high reconfigurability of light enables in-parallel high-throughput operations, which is demonstrated using two laser beams to form two particle enrichment sites in a droplet simultaneously. Finally, this light strategy is also demonstrated by concentrating cells and nucleic acid molecules. This work paves the way for the applications of optofluidics in cell sorting, point-of-care analysis, and drug screening.

Ni Single Atoms Embedded in Graphene Nanoribbon Sieves for High-Performance CO2 Reduction to CO.

Ni single-atom catalysts (SACs) are appealing for electrochemical reduction CO2 reduction (CO2 RR). However, regulating the balance between the activity and conductivity remains a challenge to Ni SACs due to the limitation of substrates structure. Herein, the intrinsic performance enhancement of Ni SACs anchored on quasi-one-dimensional graphene nanoribbons (GNRs) synthesized is demonstrated by longitudinal unzipping carbon nanotubes (CNTs). The abundant functional groups on GNRs can absorb Ni atoms to form rich Ni-N4 -C sites during the anchoring process, providing a high intrinsic activity. In addition, the GNRs, which maintain a quasi-one-dimensional structure and possess a high conductivity, interconnect with each other and form a conductive porous framework. The catalyst yields a 44 mA cm-2 CO partial current density and 96% faradaic efficiency of CO (FECO ) at -1.1 V vs RHE in an H-cell. By adopting a membrane electrode assembly (MEA) flow cell, a 95% FECO and 2.4 V cell voltage are achieved at 200 mA cm-2 current density. This work provides a rational way to synthesize Ni SACs with a high Ni atom loading, porous morphology, and high conductivity with potential industrial applications.

Microstructure Design Strategy for Molecularly Dispersed Cobalt Phthalocyanine and Efficient Mass Transport in CO2 Electroreduction.

Cobalt phthalocyanine (CoPc) has attracted particular interest owing to its excellent activity during the electrochemical CO2 conversion to CO. However, the efficient utilization of CoPc at industrially relevant current densities is still a challenge owing to its nonconductive property, agglomeration, and unfavorable conductive substrate design. Here, a microstructure design strategy for dispersing CoPc molecules on a carbon substrate for efficient CO2 transport during CO2 electrolysis is proposed and demonstrated. The highly dispersed CoPc is loaded on a macroporous hollow nanocarbon sheet to act as the catalyst (CoPc/CS). The unique interconnected and macroporous structure of the carbon sheet forms a large specific surface area to anchor CoPc with high dispersion and simultaneously boosts the mass transport of reactants in the catalyst layer, significantly improving the electrochemical performance. By employing a zero-gap flow cell, the designed catalyst can mediate CO2 to CO with a high full-cell energy efficiency of 57% at 200 mA cm-2 .

Author Correction: Analysis of the Human Protein Atlas Image Classification competition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: Analysis of the Human Protein Atlas Image Classification competition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Publisher Correction: Analysis of the Human Protein Atlas Image Classification competition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SHFL inhibits enterovirus A71 infection by triggering degradation of viral 3Dpol protein via the ubiquitin-proteasome pathway.

Enterovirus A71 (EV-A71) is a highly contagious virus that poses a major threat to global health, representing the primary etiological agent for hand-foot and mouth disease (HFMD) and neurological complications. It has been established that interferon signaling is critical to establishing a robust antiviral state in host cells, mainly mediated through the antiviral effects of numerous interferon-stimulated genes (ISGs). The host restriction factor SHFL is a novel ISG with broad antiviral activity against various viruses through diverse underlying molecular mechanisms. Although SHFL is widely acknowledged for its broad-spectrum antiviral activity, it remains elusive whether SHFL inhibits EV-A71. In this work, we validated that EV-A71 triggers the upregulation of SHFL both in cell lines and in a mouse model. Knockdown and overexpression of SHFL in EVA71-infected cells suggested that this factor could markedly suppress EV-A71 replication. Our findings further revealed an intriguing mechanism of SHFL that it could interact with the nonstructural proteins 3Dpol of EV-A71 and promoted the degradation of 3Dpol through the ubiquitin-proteasome pathway. Furthermore, the zinc-finger domain and the 36 amino acids (164-199) of SHFL were crucial to the interaction between SHFL and EV-A71 3Dpol . Overall, these findings broadened our understanding of the pivotal roles of SHFL in the interaction between the host and EV-A71.

Boosting Carbon Dioxide Reduction in a Photocatalytic Fuel Cell with a Bubbling Fluidized Cathode: Dual Function of Titanium Carbide.

Photoelectrochemical reduction of carbon dioxide (CO2) is a promising avenue to realize resourceful utilization of carbon dioxide and mitigate the energy shortage. Herein, a photocatalytic fuel cell with a bubbling fluidized cathode (PFC-BFC) is proposed to increase the performance of the photocatalytic CO2 reduction reaction (CO2RR). Titanium carbide (Ti3C2) is first used as a fluidized cathode catalyst with the dual features of superior capacitance and high CO2RR catalytic activity. Compared with the conventional PFC system, the as-proposed PFC-BFC system exhibits a higher gas production performance. Particularly, the generation rate and Faraday efficiency for CH4 production reach to 37.2 µmol g-1 h-1 and 72%, which are 10.9 and 6.5 times higher than that of the conventional PFC system, respectively. The bubbling fluidized cathode allows a rapid electron transfer between catalysts and the current collector and an efficient diffusion of catalysts in the whole solution, thus remarkably increasing the effective reaction area of the CO2RR. In addition, the fluidized reaction mechanism of charging/discharging-coupled CO2RR is investigated. Significantly, a magnified PFC-BFC system is designed and exhibits a similar gas generation rate compared to that of the small-scale system, indicating a good potential of scaling up in the industry applications. These results demonstrated that the proposed PFC-BFC system can maximize the utilization of catalyst active sites and enhance the reaction kinetics, providing an alternative design for the application of CO2RR.