Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination.

Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.

Ubiquitin-specific proteinase 1 stabilizes PRRSV nonstructural protein Nsp1ß to promote viral replication by regulating K48 ubiquitination.

The porcine reproductive and respiratory syndrome virus (PRRSV) can lead to severe reproductive problems in sows, pneumonia in weaned piglets, and increased mortality, significantly negatively impacting the economy. Post-translational changes are essential for the host-dependent replication and long-term infection of PRRSV. Uncertainty surrounds the function of the ubiquitin network in PRRSV infection. Here, we screened 10 deubiquitinating enzyme inhibitors and found that the ubiquitin-specific proteinase 1 (USP1) inhibitor ML323 significantly inhibited PRRSV replication in vitro. Importantly, we found that USP1 interacts with nonstructural protein 1ß (Nsp1ß) and deubiquitinates its K48 to increase protein stability, thereby improving PRRSV replication and viral titer. Among them, lysine at position 45 is essential for Nsp1ß protein stability. In addition, deficiency of USP1 significantly reduced viral replication. Moreover, ML323 loses antagonism to PRRSV rSD16-K45R. This study reveals the mechanism by which PRRSV recruits the host factor USP1 to promote viral replication, providing a new target for PRRSV defense.IMPORTANCEDeubiquitinating enzymes are critical factors in regulating host innate immunity. The porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1ß (Nsp1ß) is essential for producing viral subgenomic mRNA and controlling the host immune system. The host inhibits PRRSV proliferation by ubiquitinating Nsp1ß, and conversely, PRRSV recruits the host protein ubiquitin-specific proteinase 1 (USP1) to remove this restriction. Our results demonstrate the binding of USP1 to Nsp1ß, revealing a balance of antagonism between PRRSV and the host. Our research identifies a brand-new PRRSV escape mechanism from the immune response.

VP3 protein of Senecavirus A promotes viral IRES-driven translation and attenuates innate immunity by specifically relocalizing hnRNPA2B1.

Viruses deploy sophisticated strategies to hijack the host's translation machinery to favor viral protein synthesis and counteract innate cellular defenses. However, little is known about the mechanisms by which Senecavirus A (SVA) controls the host's translation. Using a series of sophisticated molecular cell manipulation techniques, heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) was identified as an essential host factor involved in translation control in SVA-infected cells. It was also determined that the SVA structural protein, VP3, binds to and relocalizes hnRNPA2B1, which interferes with the host's protein synthesis machinery to establish a cellular environment that facilitates viral propagation via a two-pronged strategy: first, hnRNPA2B1 serves as a potent internal ribosome entry site (IRES) trans-acting factor, which is selectively co-opted to promote viral IRES-driven translation by supporting the assembly of translation initiation complexes. Second, a strong repression of host cell translation occurs in the context of the VP3-hnRNPA2B1 interaction, resulting in attenuation of the interferons response. This is the first study to demonstrate the interaction between SVA VP3 and hnRNPA2B1, and to characterize their key roles in manipulating translation. This novel dual mechanism, which regulates selective mRNA translation and immune evasion of virus-infected cells, highlights the VP3-hnRNPA2B1 complex as a potential target for the development of modified antiviral or oncolytic reagents. IMPORTANCE: Viral reproduction is contingent on viral protein synthesis, which relies entirely on the host's translation machinery. As such, viruses often need to control the cellular translational apparatus to favor viral protein production and avoid host innate defenses. Senecavirus A (SVA) is an important virus, both as an emerging pathogen in the pork industry and as a potential oncolytic virus for neuroendocrine cancers. Here, heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) was identified as a critical regulator of the translational landscape during SVA infection. This study supports a model whereby the VP3 protein of SVA efficiently subverts the host's protein synthesis machinery through its ability to bind to and relocalize hnRNPA2B1, not only selectively promoting viral internal ribosome entry site-driven translation but also resulting in global translation shutdown and immune evasion. Together, these data provide new insights into how the complex interactions between translation machinery, SVA, and innate immunity contribute to the pathogenicity of the SVA.

Transposon molecular domestication and the evolution of the RAG recombinase.

Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1-RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates-arginine 848 in RAG1 and an acidic region in RAG2-that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.

Thyroid hormone receptor-beta agonist HSK31679 alleviates MASLD by modulating gut microbial sphingolipids.

BACKGROUND & AIMS: As the first approved medication for metabolic dysfunction-associated steatohepatitis (MASH), the thyroid hormone receptor-ß (THR-ß) agonist MGL-3196 (resmetirom) has garnered much attention as a liver-directed, bioactive oral drug. However, studies on MGL-3196 have also identified remarkable heterogeneity of individual clinical efficacy and its interference with gut microbiota in host hepatoenteral circulation remains to be elucidated. METHODS: We compared MASH attenuation by MGL-3196 and its derivative drug HSK31679 between germ-free (GF) and specific-pathogen free (SPF) mice to evaluate the role of gut microbiota. Then cross-omics analyses of microbial metagenome, metabolome and single-cell RNA-sequencing were applied to a randomized, double-blind, placebo-controlled multiple ascending dose cohort receiving HSK31679 treatment (n = 32) or placebo (n = 8), to comprehensively investigate the altered gut microbiota metabolism and circulating immune signatures. RESULTS: HSK31679 outperformed MGL-3196 in ameliorating MASH diet-induced steatohepatitis of SPF mice but not GF mice. In the multiple ascending dose cohort of HSK31679, the relative abundance of B. thetaiotaomicron was significantly enriched, impairing glucosylceramide synthase (GCS)-catalyzed monoglucosylation of microbial Cer(d18:1/16:0) and Cer(d18:1/24:1). In contrast to the non-inferior effect of MGL-3196 and HSK31679 on MASH resolution in GFBTΔGCS mice, HSK31679 led to superior benefit on steatohepatitis in GFBTWT mice, due to its steric hindrance of R123 and Y401 of gut microbial GCS. For participants with high fecal GCS activity, the administration of 160 mg HSK31679 induced a shift in peripheral compartments towards an immunosuppressive niche, characterized by decreased CD8α+ dendritic cells and MINCLE+ macrophages. CONCLUSIONS: This study provided novel insights into the gut microbiota that are key to the efficacy of HSK31679 treatment, revealing microbial GCS as a potential predictive biomarker in MASH, as well as a new target for further microbiota-based treatment strategies for MASH. IMPACT AND IMPLICATIONS: Remarkable heterogeneity in individual clinical efficacy of thyroid hormone receptor-ß agonists and their interferences with the microbiome in host hepatoenteral circulation are poorly understood. In our current germ-free mouse models and a randomized, double-blind, multiple-dose cohort study, we identified microbial glucosylceramide synthase as a key mechanistic node in the resolution of metabolic dysfunction-associated steatohepatitis. Microbial glucosylceramide synthase activity could be a predictive biomarker of response to HSK31679 treatment or a new target for microbiota-based therapeutics in metabolic dysfunction-associated steatohepatitis.

Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase.

Jawed vertebrate adaptive immunity relies on the RAG1/RAG2 (RAG) recombinase, a domesticated transposase, for assembly of antigen receptor genes. Using an integration-activated form of RAG1 with methionine at residue 848 and cryo-electron microscopy, we determined structures that capture RAG engaged with transposon ends and U-shaped target DNA prior to integration (the target capture complex) and two forms of the RAG strand transfer complex that differ based on whether target site DNA is annealed or dynamic. Target site DNA base unstacking, flipping, and melting by RAG1 methionine 848 explain how this residue activates transposition, how RAG can stabilize sharp bends in target DNA, and why replacement of residue 848 by arginine during RAG domestication led to suppression of transposition activity. RAG2 extends a jawed vertebrate-specific loop to interact with target site DNA, and functional assays demonstrate that this loop represents another evolutionary adaptation acquired during RAG domestication to inhibit transposition. Our findings identify mechanistic principles of the final step in cut-and-paste transposition and the molecular and structural logic underlying the transformation of RAG from transposase to recombinase.

A Pilot Study Using Machine Learning Algorithms and Wearable Technology for the Early Detection of Postoperative Complications After Cardiothoracic Surgery.

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

Multiple Enzyme-Mimicking CuMOF-Driven Self-Cascading Antioxidant Reaction for Synergistic Electrochemiluminescence Modulation in Ultrasensitive Biosensing.

Developing nanozyme-based free radical scavenging is a promising signal modulation approach for ECL sensing. Nevertheless, the relatively low antioxidant activity and inherent pro-oxidant activity of numerous nanozymes have significantly hindered the development of this strategy. Here a biofunctional copper-based metal-organic framework (CuMOF) with multiple enzyme-mimicking activities was employed for the modulation of the ECL immunosensor, guided by the self-cascade antioxidant reaction. The inherent SOD, CAT, and the capacity to eliminate ·OH endow CuMOF with powerful synergistic antioxidant effects while little pro-oxidant activities were displayed, enabling efficient scavenging of the O2·- produced during the electrochemical oxidation of H2O2. Subsequently, the nanoconfinement effect of the layered double hydroxide was introduced to ensure a steady ECL signal. The suggested ECL immunosensor, using aflatoxin B1 as a proof-of-concept target, demonstrated a detection range spanning from 0.001 pg/mL to 10 ng/mL, with the detection limit calculated to be 0.18 fg/mL. This exceptional achievement greatly broadens the range of possible uses for nanozyme-based radical scavenging modulated ECL analysis.

Intelligent Biogenic Missile for Two-Photon Fluorescence Imaging-Guided Combined Photodynamic Therapy and Chemotherapy in Tumors.

Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.

Accelerated and Guided Zn2+ Diffusion via Polarized Interface Engineering Toward High Performance Wearable Zinc-Ion Batteries.

Rechargeable aqueous Zn-ion batteries (ZIBs) are considered as a new energy storage device for wearable electronic equipment. Nowadays, dendrite growth and uneven deposition of zinc have been the principal problems to suppress the development of high-performance wearable zinc-ion batteries. Herein, a perovskite material of LaAlO3 nanoparticle has been applied for interface engineering and zinc anode protection. By adjusting transport channels and accelerating the Zn2+ diffusion, the hydrogen evolution reaction potential is improved, and electric field distribution on the Zn electrode surface is regulated to navigate the fast and uniform deposition of Zn2+. As a proof of demonstration, the assembled LAO@Zn||MnO2 batteries can display the highest capacity of up to 140 mAh g-1 without noticeable decay even after 1000 cycles. Moreover, a motor-driven fan and electronic wristwatch powered by wearable ZIBs can demonstrate the practical feasibility of LAO@Zn||MnO2 in wearable electronic equipment.

A Synergistically Regulated Cathode/Electrolyte Interphase With High Stability and Rapid Zn2+ Migration Toward Advanced Flexible Zinc-Ion Batteries.

Na3V2(PO4)3(NVP), as a representative sodium superionic conductor with a stable polyanion framework, is considered a cathode candidate for aqueous zinc-ion batteries attributed to their high discharge platform and open 3D structure. Nevertheless, the structural stability of NVP and the cathode-electrolyte interphase (CEI) layer formed on NVP can be deteriorated by the aqueous electrolyte to a certain extent, which will result in slow Zn2+ migration. To solve these problems, doping Si elements to NVP and adding sodium acetate (NaAc) to the electrolyte are utilized as a synergistic regulation route to enable a highly stable  CEI with rapid Zn2+ migration. In this regard, Ac- competitively takes part in the solvation structure of Zn2+ in aqueous electrolyte, weakening the interaction between water and Zn2+, and meanwhile a highly stable CEI is formed to avoid structural damage and enable rapid Zn2+ migration. The NVPS/C@rGO electrode exhibits a notable capacity of 115.5 mAh g-1 at a current density of 50 mA g-1 in the mixed electrolyte (3 M ZnOTF2+3 M NaAc). Eventually, a collapsible "sandwich" soft pack battery is designed and fabricated and can be used to power small fans and LEDs, which proves the practical application of aqueous zinc-ion batteries in flexible batteries.

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.

Behavioral intentions of self-isolation and informing close contacts after developing mpox-related symptoms among young men who have sex with men in China.

The 2022 multi-country mpox outbreak raised public concern globally. Self-isolation and informing close contacts after developing mpox-related symptoms are critical measures in controlling the outbreak. This study investigated behavioral intentions of self-isolation and informing close contacts after developing mpox-related symptoms and associated factors among young men who have sex with men (YMSM) aged 18-29 years in China. The cross-sectional study was conducted among 2493 YMSM in six provincial regions in China from September 10th to 30th, 2022. Descriptive and logistic analyses were applied, using the intentions of self-isolation and informing close contacts after developing mpox-related symptoms as binary outcomes. The mean age of the participants was 24.6 (SD = 2.9) years. The prevalence of having intentions of self-isolation and informing close contacts after developing mpox-related symptoms was 88.6% (95% CI: 87.3%-89.9%) and 84.9% (95% CI: 83.5%-86.3%). Participants who were employed (adjusted odds ratio (AOR) = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI:1.002, 1.876), had higher mpox knowledge scores (AOR = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI: 1.002-1.876), and had higher perceived threats of mpox (AOR = 1.079, 95% CI: 1.030-1.130; AOR = 1.045, 95% CI: 1.002-1.090) were more likely to intend to self-isolate and inform close contacts. Participants who had MSM in-person gatherings in the past 6 months were more likely to intend to self-isolate (AOR = 1.392, 95% CI: 1.066-1.208). Participants with higher depression scores (AOR = 0.968, 95% CI: 0.948-0.989) and self-stigma (AOR = 0.975, 95% CI: 0.954-0.997) were less likely to intend to self-isolate and inform close contacts, respectively. Self-isolation and informing close contacts when developing disease-related symptoms are acceptable measures in response to mpox in China. Strengthening targeted risk communication and self-efficacy, raising disease knowledge, providing mental support, and reducing stigma toward the affected community are warranted.

Genome-wide association studies reveal novel loci for grain size in two-rowed barley (Hordeum vulgare L.).

KEY MESSAGE: SNP-based and InDel-based GWAS on multi-environment data identified genomic regions associated with barley grain size. Barley yield and quality are greatly influenced by grain size. Improving barley grain size in breeding programs requires knowledge of genetic loci and alleles in germplasm resources. In this study, a collection of 334 worldwide two-rowed barley accessions with extensive genetic diversity was evaluated for grain size including grain length (GL), grain width (GW), and thousand-grain weight (TGW) across six independent field trials. Significant differences were observed in genotype and environments for all measured traits. SNP- and InDel-based GWAS were applied to dissect the genetic architecture of grain size with an SLAF-seq strategy. Two approaches using the FarmCPU model revealed 38 significant marker-trait associations (MTAs) with PVE ranging from 0.01% to 20.68%. Among these MTAs, five were on genomic regions where no previously reported QTL for grain size. Superior alleles of TGW-associated SNP233060 and GL-associated InDel11006 exhibited significantly higher levels of phenotype. The significant MTAs could be used in marker-assisted selection breeding.

The moderating role of resilience in the association between workload and depressive symptoms among radiology residents in China: results from a nationwide cross-sectional study.

OBJECTIVES: The current study aimed to explore the moderating role of psychological resilience in the association between workload and depressive symptoms among radiology residents during standardized residency training (SRT) in China. METHODS: A nationwide cross-sectional online survey was conducted among radiology residents in China. Workload was measured by working hours per week and the frequency of frontline nightwork in the last month. Resilience was assessed by the 2-item Connor-Davidson Resilience Scale. Depressive symptoms were measured by the Depression Anxiety Stress Scales. The hierarchical regression and simple slope analyses were performed to examine the moderating effect of resilience. RESULTS: Among 3666 radiology residents, the mean age was 27.3 years (SD = 2.6) and 58% were female. About 24.4% of the participants reported medium to severe depressive symptoms. The hierarchical regression showed that working hours (ba = 0.11, 95%CI: 0.08, 0.14) and having frontline nightwork more than once (ba = 1.22, 95%CI: 0.67, 1.78) were positively associated with depressive symptoms; the moderating effect of resilience was significant in the association of depressive symptoms with working hours (ba = - 0.02, 95%CI: - 0.03, - 0.01) and having frontline nightwork more than once (ba = - 0.28, 95%CI: - 0.49, - 0.07). The simple slope test showed the association between workload-related variables and depressive symptoms was only significant in those with a relatively lower level of resilience. CONCLUSIONS: The study found that resilience was an important modifier buffering the positive association between workload and depressive symptoms among radiology residents in China. Future medical training programs are suggested to include effective intervention components to increase personal resilience. CLINICAL RELEVANCE STATEMENT: Heavy workload in clinical setting may pose adverse effect on mental health and job performance of radiology residents. The study investigated whether psychological resilience would mitigate the association between workload and depressive symptoms among Chinese radiology residents. KEY POINTS: • Radiology residents with a heavier workload presented a higher level of depressive symptoms in China. • Psychological resilience mitigated the positive association between workload and depressive symptoms. • The association between workload and depressive symptoms was only statistically significant in radiology residents with a relatively lower level of resilience.

Cooling Condition Effect on Spectral Properties and Smartphone-Based Anticounterfeiting Application of Zn3Ga2Ge2O10/Cr3+ Phosphors.

The influence of cooling history for the Zn3Ga2Ge2O10/Cr3+ phosphors prepared by solid state reaction on the spectral properties was discovered, and an anticounterfeiting scheme based on the identification with smartphone was proposed and experimentally demonstrated using the studied phosphors. A combination of color-tunable visible fluorescence emission and near-infrared (NIR) afterglow emission in Zn3Ga2Ge2O10/x mol % Cr3+(x = 0, 0.05, 1, 2, 3, and 4) phosphors to achieve multimode anticounterfeiting was reported. It is found that with the increasing Cr3+ concentrations, the visible emission can be tuned from green, light pink, and light red to deep red under 254 nm ultraviolet (UV) excitation. This phenomenon is related to the formation of oxygen vacancies in the host during the process of natural cooling and the characteristic emission of Cr3+. In addition, the persistent time of the Cr3+ emission centered at 700 nm can be also tuned by various Cr3+ concentrations. A possible mechanism was deduced to explain the afterglow phenomenon. Lastly, a flower pattern applied in anticounterfeiting was fabricated using the Zn3Ga2Ge2O10/x mol % Cr3+ (x = 0, 0.05, 1, 2, 3, and 4) phosphors to present tunable color and NIR afterglow signals at different excitation modes, and the camera of smartphone was chosen as a detection tool to take the NIR images. The results obtained above suggest that the prepared phosphors at natural cooling condition have great potential in affording advanced optical anticounterfeiting.

Genome-wide identification and expression analysis of the WNK kinase gene family in soybean.

WNK kinases are a unique class of serine/threonine protein kinases that lack a conserved catalytic lysine residue in the kinase domain, hence the name WNK (with no K, i.e., lysine). WNK kinases are involved in various physiological processes in plants, such as circadian rhythm, flowering time, and stress responses. In this study, we identified 26 WNK genes in soybean and analyzed their phylogenetic relationships, gene structures, chromosomal distribution, cis-regulatory elements, expression patterns, and conserved protein motifs. The soybean WNK genes were unevenly distributed on 15 chromosomes and underwent 21 segmental duplication events during evolution. We detected 14 types of cis-regulatory elements in the promoters of the WNK genes, indicating their potential involvement in different signaling pathways. The transcriptome database revealed tissue-specific and salt stress-responsive expression of WNK genes in soybean, the second of which was confirmed by salt treatments and qRT-PCR analysis. We found that most WNK genes were significantly up-regulated by salt stress within 3 h in both roots and leaves, except for WNK5, which showed a distinct expression pattern. Our findings provide valuable insights into the molecular characteristics and evolutionary history of the soybean WNK gene family and lay a foundation for further analysis of WNK gene functions in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01440-5.

Construction of controlled hyper-crosslinked nanofibrous tubes for Cr(VI) removal: Response surface, kinetics, and isotherm.

Porous organic polymers (POPs) exhibit significant potential for adsorbing toxic metal ions in wastewater. Developing POPs with controlled morphologies is a pivotal direction in this field. This study synthesized a series of novel hyper-crosslinked nanofibrous tubes designated HCNT-Cn (n = 4, 8, 12, 16) via Friedel-Crafts alkylation and quaternization reactions. These reactions were fine-tuned through a post-synthetic strategy involving varying alkyl chain lengths. These materials were characterized using FT-IR, SEM, N2 adsorption-desorption isotherms, among others, and they were specifically evaluated for their ability to adsorb Cr(VI). Among the variants, HCNT-C4 exhibited the highest specific surface area (495.26 m2 g-1), superior hydrophilicity (CA = 48.7°), and optimal adsorption performance. The adsorption kinetics of HCNT-C4 conformed to a pseudo-second-order model, while its adsorption isotherm aligned with the Langmuir model. An investigation into the impact of Cr(VI) removal was conducted using three independent variables in a Central Composite Design (CCD) response surface model, revealing that under optimal conditions, the Cr(VI) removal efficiency reached 98%. Additionally, a mechanism for Cr(VI) adsorption on HCNT-C4 was proposed. It was also found that HCNT-C4 could be reused up to four times, maintaining a removal efficiency of 70%. This study suggests potential applications for removing Cr(VI) from contaminated wastewater.

Correlation between tumor budding and the long-term follow-up outcomes after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. METHODS: We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). RESULTS: A total of 437 patients were enrolled [154 TB and 283 no tumor budding (NTB)], and 258 patients (52 TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5 years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. CONCLUSION: TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.

SP2509, a specific antagonist of LSD1, exhibits antiviral properties against Porcine epidemic diarrhea virus.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV), a type of coronavirus, is one of the main pathogens that can infect pigs of all ages. It causes diarrhea and acute death of newborn piglets, resulting in massive economic losses to the worldwide swine industry. While vaccination remains the primary approach in combating PEDV, it often fails to address all the challenges posed by the infection, particularly in light of the emergence of evolving mutant strains. Therefore, there is a critical need to identify potent antiviral drugs that can effectively safeguard pigs against PEDV infection. RESULTS: In this study, the antiviral efficacy of SP2509, a specific antagonist of Lysine-specific demethylase 1(LSD1), was evaluated in vitro. The RT-qPCR, Western blot, TCID50, and IFA showed that at a concentration of 1µmol/L, SP2509 significantly inhibited PEDV infection. Additionally, viral life cycle assays showed that SP2509 operates by impeding PEDV internalization and replication rather than attachment and release. Regarding mechanism, in Huh-7 cells, knockdowns LSD1 can suppress PEDV replication. This indicated that the inhibition effect of SP2509 on PEDV largely depends on the activity of its target protein, LSD1. CONCLUSION: Our results in vitro show that SP2509 can inhibit PEDV infection during the internalization and replication stage and revealed a role of LSD1 as a restriction factor for PEDV. These imply that LSD1 might be a target for interfering with the viral infection, and SP2509 could be developed as an effective anti-PEDV agent.