Excitation power-dependent multicolor upconversion in NaLnF4:Er3+ under 1532†nm irradiation for anti-counterfeiting application.

Upconversion (UC) materials are renowned for their ability to convert low-energy photons into high-energy ones. The manipulation of parameters allows for the observation of multicolored UC luminescence (UCL) within a single material system. While modulation of multicolored UCL commonly relies on excitation at approximately 980 nm, investigation into multicolored UC materials activated by a 1532 nm excitation source remains comparatively scarce. In this work, we introduce NaLnF4:Er3+ as a novel class of smart luminescent materials. When the power density of a 1532 nm laser increases from 0.5 to 20.0 W/cm2, the emission peak positions remain unchanged, but the red-to-green (R/G) ratio decreases significantly from 18.82 to 1.48, inducing a color shift from red to yellow and ultimately to green. In contrast, no color variation is observed when NaLnF4:Er3+ is excited with a 980 nm laser at different power densities. This power-dependent multicolored UCL of NaLnF4:Er3+ excited at 1532 nm can be attributed to the competitive processes of upward pumping and downward relaxation of electrons on the 4I9/2 level of Er3+. By utilizing the unique UC characteristics of NaLnF4:Er3+, its potential utility in anti-counterfeiting applications is demonstrated. Our research highlights the distinctive optical properties of NaLnF4:Er3+ and provides novel insights into the use of luminescent materials in optical anti-counterfeiting technologies.

Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

Boosting the mono-axial crystal field in stable high-coordinate Dy(III) single-ion magnets by substitution of the phenoxy axial ligand.

Synthesis of air-stable and high-performance single-molecule magnets (SMMs) is challenging. Here, a heptadentate pentapyridyldiamine (BPA-TPA) ligand and fine-tuned axial phenoxy ligands are used to synthesize two triangular dodecahedral Dy(III) complexes [Dy(BPA-TPA)(4-methoxy-PhO)](BPh4)2·3CH2Cl2 (4) and [Dy(BPA-TPA)(2,4-dimethyl-PhO)](BPh4)2·0.85CH2Cl2 (5). Both complexes have high effective barriers exceeding 400 K and magnetic hysteresis up to 8 K, which is ascribed to one strong and short Dy-O bond combined with seven weak Dy-N bonds. Ab initio calculations reveal the thermally activated quantum tunneling of magnetization through the first excited Kramers doublet, due to the presence of a strong axial Dy-O crystal ligand. Substitution of the phenoxy ligand leads to more constrained vibrations, improving the magnetic hysteresis behavior for 5.

Modeling kidney development, disease, and plasticity with clonal expandable nephron progenitor cells and nephron organoids.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here we report manipulation of p38 and YAP activity creates a synthetic niche that allows the long-term clonal expansion of primary mouse and human NPCs, and induced NPCs (iNPCs) from human pluripotent stem cells. Cultured iNPCs resemble closely primary human NPCs, generating nephron organoids with abundant distal convoluted tubule cells, which are not observed in published kidney organoids. The synthetic niche reprograms differentiated nephron cells into NPC state, recapitulating the plasticity of developing nephron in vivo. Scalability and ease of genome-editing in the cultured NPCs allow for genome-wide CRISPR screening, identifying novel genes associated with kidney development and disease. A rapid, efficient, and scalable organoid model for polycystic kidney disease was derived directly from genome-edited NPCs, and validated in drug screen. These technological platforms have broad applications to kidney development, disease, plasticity, and regeneration.

Approaches to kidney replacement therapies-opportunities and challenges.

One out of seven people develop chronic kidney disease (CKD). When kidney function continues to decline, CKD patients may develop end-stage renal disease (ESRD, or kidney failure). More than 2 out of 1,000 adults develop ESRD and these patients must live on dialysis or get a kidney transplant to survive. Each year, more than $51 billion is spent to treat patients with ESRD in the United States. In addition, ESRD greatly reduces longevity and quality of life for patients. Compared to dialysis, kidney transplant offers the best chance of survival, but few donor organs are available. Thus, there is an urgent need for innovative solutions that address the shortage of kidneys available for transplantation. Here we summarize the status of current approaches that are being developed to solve the shortage of donor kidneys. These include the bioartificial kidney approach which aims to make a portable dialysis device, the recellularization approach which utilizes native kidney scaffold to make an engineered kidney, the stem cell-based approach which aims to generate a kidney de novo by recapitulating normal kidney organogenesis, the xenotransplantation approach which has the goal to make immunocompatible pig kidneys for transplantation, and the interspecies chimera approach which has potential to generate a human kidney in a host animal. We also discuss the interconnections among the different approaches, and the remaining challenges of translating these approaches into novel therapies.

Cytoplasmic Tail Truncation of SARS-CoV-2 Spike Protein Enhances Titer of Pseudotyped Vectors but Masks the Effect of the D614G Mutation.

The high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein-pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV), and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have examined whether such a modification also impacts the protein's function. Here, we optimized concentration methods for SARS-CoV-2 Spike-pseudotyped VSV vectors, finding that tangential flow filtration produced vectors with more consistent titers than ultracentrifugation. We also examined the impact of Spike tail truncation on transduction of various cell types and sensitivity to convalescent serum neutralization. We found that tail truncation increased Spike incorporation into both LV and VSV vectors and resulted in enhanced titers but had no impact on sensitivity to convalescent serum. In addition, we analyzed the effect of the D614G mutation, which became a dominant SARS-CoV-2 variant early in the pandemic. Our studies revealed that, similar to the tail truncation, D614G independently increases Spike incorporation and vector titers, but this effect is masked by also including the cytoplasmic tail truncation. Therefore, the use of full-length Spike protein, combined with tangential flow filtration, is recommended as a method to generate high titer pseudotyped vectors that retain native Spike protein functions. IMPORTANCE Pseudotyped viral vectors are useful tools to study the properties of viral fusion proteins, especially those from highly pathogenic viruses. The Spike protein of SARS-CoV-2 has been investigated using pseudotyped lentiviral and VSV vector systems, where truncation of its cytoplasmic tail is commonly used to enhance Spike incorporation into vectors and to increase the titers of the resulting vectors. However, our studies have shown that such effects can also mask the phenotype of the D614G mutation in the ectodomain of the protein, which was a dominant variant arising early in the COVID-19 pandemic. To better ensure the authenticity of Spike protein phenotypes when using pseudotyped vectors, we recommend using full-length Spike proteins, combined with tangential flow filtration methods of concentration if higher-titer vectors are required.