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The upconversion efficiency could be affected by Li + ions with changing the local crystal field of nanoparticles. Therefore, a series of NaGdF 4 :Yb 3+ /Tm 3+ micro-particles with different Li + doping concentrations were synthesized and investigated, respectively. The structure and morphology of the synthesized materials were tested by X-ray diffraction and scanning electron microscope. The photoluminescence properties were studied with different concentrations Li + ions doping under the irradiation of 980 nm laser. The emission peaks of Tm 3+ ions are 449, 477, 645, 723, 800 nm which are attributed to high excited states to ground state 3 H 6 transition through a multiple steps resonance energy transfer from excited Yb 3+ . The enormous increase in upconversion emission in upconversion micro-particles (UCMPs) by introducing Li + ions was observed by the naked eye. The strongest photoluminescence intensity is the sample with 2.5% doped Li + ions. Additionally, the practicality of the resultant UCMPs for photoluminescence visible imaging was systematically investigated. These results suggest that the Li + doped NaGdF 4 : Yb 3+ /Tm 3+ is very promising as a screen printing material for anti-counterfeiting recognition.

KY3F10:Yb3+, Tm3+ upconversion microparticles (UCMPs) with varying Mn2+ doping concentrations were synthesized via a hydrothermal method. Under 980 nm laser excitation, the sample with 3 mol% Mn2+ doping demonstrated markedly enhanced luminescence performance, exhibiting a significant intensity increase compared to undoped samples. The as-synthesized UCMPs were successfully incorporated into an anti-counterfeiting ink. Target information was encrypted using a hash function to generate a QR code, which was then screen-printed onto substrate materials. Under 980 nm laser irradiation, the printed QR code exhibited visible blue fluorescence with high stability, confirming its anti-counterfeiting capability. Furthermore, an image recognition system for anti-counterfeiting, based on a hybrid Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) architecture, was developed on the Matlab platform. The system achieved 100% recognition accuracy for the luminescent QR code patterns, providing valuable insights for the development of deep learning-based image anti-counterfeiting technologies.

Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases and determine their complex structures with their respective targets. Furthermore, we show that applying inhibitors simultaneously that block both entry pathways has a synergistic antiviral effect. Notably, we devise a bispecific compound, 212-148 , exhibiting the dual-inhibition ability of both TMPRSS2 and CTSL/CTSB, and demonstrate antiviral activity against various SARS-CoV-2 variants with different viral entry profiles. Our findings offer an alternative approach for the discovery of SARS-CoV-2 antivirals, as well as application for broad-spectrum treatment of viral pathogenic infections with similar entry pathways. TMPRSS2 and CTSL/CTSB, host proteases that facilitate SARS-CoV-2 entry, are promising drug targets. Here the authors simultaneously inhibit these host proteases and see synergistic antiviral effects, offering a broad-spectrum intervention against SARS-CoV-2 variants.

Pendrin (SLC26A4) is an anion exchanger expressed in the apical membranes of selected epithelia. Pendrin ablation causes Pendred syndrome, a genetic disorder associated with sensorineural hearing loss, hypothyroid goiter, and reduced blood pressure. However its molecular structure has remained unknown, limiting our understanding of the structural basis of transport. Here, we determine the cryo-electron microscopy structures of mouse pendrin with symmetric and asymmetric homodimer conformations. The asymmetric homodimer consists of one inward-facing protomer and the other outward-facing protomer, representing coincident uptake and secretion- a unique state of pendrin as an electroneutral exchanger. The multiple conformations presented here provide an inverted alternate-access mechanism for anion exchange. The structural and functional data presented here disclose the properties of an anion exchange cleft and help understand the importance of disease-associated variants, which will shed light on the pendrin exchange mechanism. Pendrin SLC26A4 plays an important role for anion balance. Here, authors resolve cryo-EM structures of pendrin performing co-incident uptake and secretion of anions, providing a structural basis of this anion exchange mechanism.

The Omicron subvariants BQ.1.1, XBB.1.5, and XBB.1.16 of SARS-CoV-2 are known for their adeptness at evading immune responses. Here, we isolate a neutralizing antibody, 7F3, with the capacity to neutralize all tested SARS-CoV-2 variants, including BQ.1.1, XBB.1.5, and XBB.1.16. 7F3 targets the receptor-binding motif (RBM) region and exhibits broad binding to a panel of 37 RBD mutant proteins. We develop the IgG-like bispecific antibody G7-Fc using 7F3 and the cross-neutralizing antibody GW01. G7-Fc demonstrates robust neutralizing activity against all 28 tested SARS-CoV-2 variants and sarbecoviruses, providing potent prophylaxis and therapeutic efficacy against XBB.1 infection in both K18-ACE and BALB/c female mice. Cryo-EM structure analysis of the G7-Fc in complex with the Omicron XBB spike (S) trimer reveals a trimer-dimer conformation, with G7-Fc synergistically targeting two distinct RBD epitopes and blocking ACE2 binding. Comparative analysis of 7F3 and LY-CoV1404 epitopes highlights a distinct and highly conserved epitope in the RBM region bound by 7F3, facilitating neutralization of the immune-evasive Omicron variant XBB.1.16. G7-Fc holds promise as a potential prophylactic countermeasure against SARS-CoV-2, particularly against circulating and emerging variants. In this study, the authors develop a potent bispecific antibody targeting two epitopes within the SARS-CoV-2 receptor binding domain and showing robust prophylactic and therapeutic efficacy against XBB.1 infection in mice.

Climate warming profoundly affects plant biodiversity, community productivity, and soil properties in alpine and subalpine grassland ecosystems. However, these effects are poorly understood across elevational gradients in subalpine meadow ecosystems. To reveal the elevational patterns of warming effects on plant biodiversity, community structure, productivity, and soil properties, we conducted a warming experiment using open-top chambers from August 2019 to August 2022 at high (2764 m a. s. l.), medium (2631 m a. s. l.), and low (2544 m a. s. l.) elevational gradients on a subalpine meadow slope of Mount Wutai, Northern China. Our results showed that three years of warming significantly increased topsoil temperature but significantly decreased topsoil moisture at all elevations ( P <0.05), and the percentage of increasing temperature and decreasing moisture both gradually raised with elevation lifting. Warming-induced decreasing proportions of soil organic carbon (SOC, by 19.24%), and total nitrogen (TN, by 24.56%) were the greatest at high elevational gradients. Experimental warming did not affect topsoil C: N, pH, NO 3 − -N, or NH 4 + -N at the three elevational gradients. Warming significantly increased species richness ( P <0.01) and Shannon-Weiner index ( P <0.05) at low elevational gradients but significantly decreased belowground biomass ( P <0.05) at a depth of 0–10 cm at three elevational gradients. Warming caused significant increases in the aboveground biomass in the three elevational plots. Warming significantly increased the aboveground biomass of graminoids in medium (by 92.47%) and low (by 98.25%) elevational gradients, that of sedges in high (by 72.44%) and medium (by 57.16%) elevational plots, and that of forbs in high (by 75.88%), medium (by 34.38%), and low (by 74.95%) elevational plots. Species richness had significant linear correlations with SOC, TN, and C: N ( P <0.05), but significant nonlinear responses to soil temperature and soil moisture in the warmed treatment ( P <0.05). The warmed aboveground biomass had a significant nonlinear response to soil temperature and significant linear responses to soil moisture ( P <0.05). This study provided evidence that altitude is a factor in sensitivity to climate warming, and these different parameters (e.g., plant species richness, Shannon-Weiner index, soil temperature, soil moisture, SOC, and TN) can be used to measure this sensitivity.

PurposeTo compare the diagnostic value of curved planar reformation of MRI (MRI-CPR) and 2D MRI in determining the responsible nerve in patients with adult lumbar degenerative scoliosis (ALDS).MethodA total of 45 patients diagnosed with ALDS were included in the study. All patients underwent MRI-CPR and 2D MRI and subsequently received surgery. These two diagnostic methods were compared with the results of surgical exploration to assess nerve root compression.ResultsThe sensitivity and accuracy of MRI-CPR are higher than 2D MRI (93.8% vs 80.0%; 92.8% vs 77.7%, respectively). And the specificity of MRI-CPR is higher than 2D MRI (87.5% vs 68.8%). Besides, the PPV and NPV of MRI-CPR are higher than 2D MRI (96.8% vs 91.2%; 7.8.% vs 45.8%). The area (AUC) under the receiver operating characteristic curve (ROC) for MRI-CPR and 2D MRI was 0.74 and 0.91, respectively. The judgement was made by two independent radiologists, while the consistency tests for 2D MRI and MRI-CPR with Kappa values were 90.6% and 82.2%, respectively.ConclusionsThe clinical diagnostic value of MRI-CPR was better than 2D MRI in the determination of the responsible nerve root. Moreover, MRI-CPR sequence images can clearly show the route of lumbosacral nerve roots and their relationship with adjacent tissues. Therefore, MRI-CPR can be an important complement to conventional 2D MRI in the diagnosis of responsible nerve roots in patients with ALDS.

Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability. Specificity is provided by the substrate receptor KBTBD2, which recruits p85α to the cullin3–RING E3 ubiquitin ligase (CRL3). CRL3 KBTBD2 forms multimers, which disassemble into dimers upon substrate binding (CRL3 KBTBD2 –p85α) and/or neddylation by the activator NEDD8 (CRL3 KBTBD2 ~N8), leading to p85α ubiquitination and degradation. Deactivation involves dissociation of NEDD8 mediated by the COP9 signalosome and displacement of KBTBD2 by the inhibitor CAND1. The hereby identified structural basis of p85α regulation opens the way to better understanding disturbances of glucose regulation, growth and cancer. Here, upon obtaining cryo-EM structures of CRL3 KBTBD2 in seven states, the authors propose a model for the activation cycle of CRL3 ligases, including assembly, substrate recruitment, (de)neddylation and CAND1-mediated substrate receptor exchange.