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GaInAsSb absorbers and AlGaAsSb multipliers for 2- <b> <i>μ</i> </b> m separate absorption charge and multiplication avalanche photodiodes
Ga0.71In0.29As0.25Sb0.75 and Al0.85Ga0.15As0.07Sb0.93 layers were grown on GaSb (100) substrates and characterized as candidate absorber and multiplier materials for 2 μm separate absorption, charge, and multiplication (SACM) avalanche photodiodes (APDs). The Ga0.71In0.29As0.25Sb0.75 p–i–n structures exhibited smooth surface morphology with a root mean square (RMS) roughness of 1.43 Å and photoluminescence centered at 2.37 μm. Capacitance–voltage analysis determined that the unintentionally doped absorber is n-type with a background concentration of 3.5 ± 0.5 × 1015 cm−3. Dark current measurements across varying mesa diameters showed a clear perimeter dependence, indicating dominant surface leakage. The Al0.85Ga0.15As0.07Sb0.93 n–i–p multipliers demonstrated good crystalline quality with RMS surface roughness below 2 Å. Capacitance–voltage measurements identified p-type behavior with a background doping of 2.5 ± 0.5 × 1016 cm−3. Variable-area diode analysis showed that 96%–99% of the total dark current originates from surface leakage. These results provide baseline electrical and structural parameters for future GaSb-lattice SACM APD design and highlight the need for improved control of background doping and surface passivation.
Comparative effects of SGLT2 inhibitors and GLP-1 receptor agonists on osteoarthritis risk in patients with type 2 diabetes mellitus: A multi-institutional cohort study
Objectives Sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated metabolic and anti-inflammatory benefits, which may influence the risk of osteoarthritis (OA) in patients with type 2 diabetes mellitus (T2DM). However, their comparative impact on OA incidence remains unclear. This study aimed to evaluate and compare the effects of SGLT2 inhibitors and GLP-1 RAs on the risk of developing OA in patients with T2DM. Methods A retrospective cohort study was conducted using the TriNetX database, including adults with T2DM who were newly prescribed either SGLT2 inhibitors or GLP-1 RAs between January 2017 and December 2019. After propensity-score matching, 452,445 patients were included in each group. The primary outcome was OA incidence over five years. Secondary outcomes included knee OA, hip OA, total knee arthroplasty (TKA), total hip arthroplasty (THA), and major joint injections. Results The SGLT2 inhibitor group had a significantly lower risk of OA compared with the GLP-1 RAs group (HR, 0.921; 95% CI, 0.895–0.946), with a greater reduction observed for knee OA (HR, 0.831; 95% CI, 0.783–0.882). No significant differences were observed in THA or TKA risk. SGLT2 inhibitor users also had fewer major joint injections (HR, 0.915; 95% CI, 0.882–0.951). Conclusions Among patients with T2DM, SGLT2 inhibitors were associated with a lower risk of OA, particularly knee OA and joint injections, compared to GLP-1 RAs. These findings support further investigation into the potential association between SGLT2 inhibitor use and lower OA-related outcomes.
High-performance Ka-band AlN-buffer GaN HEMTs with enhanced dynamic and breakdown characteristics achieving 10.05 W/mm <i>P</i> sat and 53.05% PAE
This work presents a high-performance Ka-band GaN high electron mobility transistor (HEMT) utilizing an undoped AlN buffer layer to replace the conventional Fe-doped GaN buffer. This AlN-buffer structure eliminates deep-level traps associated with Fe doping, leading to improved dynamic performance. Drain current transient measurements under semi-on state stress show a current collapse of 8.5% for the AlN-buffer HEMT (AlN-B HEMT), lower than the 15.7% observed in the Fe-doped GaN buffer HEMT (GaN-B HEMT). Furthermore, the wide bandgap and high critical field of AlN effectively enhance channel confinement and breakdown voltage. Compared to the conventional GaN-B HEMT, the AlN-B HEMT demonstrates a notably higher off-state breakdown voltage (124 vs 67 V) and lower off-state leakage. Large-signal characterization at 30 GHz demonstrates that the scaled AlN-B HEMT achieves a saturated output power density of 10.05 W/mm and a peak power-added efficiency of 53.05% at a drain bias of 25 V. This performance is competitive with state-of-the-art N-polar GaN HEMTs, confirming the undoped AlN-buffer structure as a highly promising pathway for developing high-performance power amplifiers in the Ka-band.
Multi-spatial resolution hyperspectral image change detection network integrating feature difference structure
Change detection (CD) can detect changes in the earth’s surface. However, the existing Siamese network-based CD methods usually calculate the Euclidean distance (ED) between two branches to obtain difference features, ignoring the deeper feature disparities captured by the CNN. In addition, the patch obtained in the CD method using spatial information may have the phenomenon that the adjacent pixels and the pixels to be classified are not the same object or change type. To deal with the aforementioned challenges, we propose FDS-BINet, a multi-spatial resolution network integrating a Feature Difference Structure (FDS) and Bicubic Interpolation (BI). The FDS module progressively extracts deep pixel-level differences through residual-enhanced Siamese branches, while BI interpolates the absolute distance spectrum to recover subpixel-level changes. The main contributions of this article are as follows: 1) A change detection framework called FDS-BINet has been proposed that fuses pixel-level and subpixel-level change information. 2) A feature difference structure (FDS) is designed to obtain deep difference features of pixel-level spatial information of bitemporal HSIs; 3) The bicubic interpolation (BI) algorithm is used for absolute distance (AD) spectrum interpolation. We can effectively boost the spatial resolution of AD spectrum data, enabling us to extract feature differences at the subpixel level from bitemporal hyperspectral images (HSIs). The experimental results demonstrate that the proposed FDS-BINet has better performance compared with representative methods in the field of HSI CD.
Total Chemical Synthesis of Interleukin‐15 and Interleukin‐2: Taming Protein Hydrophobicity and Aggregation by a Versatile Solubilizing Strategy
ABSTRACT Hydrophobic and aggregation‐prone proteins still present obstacles for protein chemical synthesis and engineering. The chemical synthesis of Interleukin‐15 (IL‐15) is a formidable challenge due to inherent sequence hydrophobicity and severe peptide aggregation, which impedes downstream protein engineering and chemical biology studies. Here, we report the first total synthesis of IL‐15 using a versatile solubilizing strategy (RST‐2.0), which enables the preparation and ligation of aggregation‐prone segments while being readily removable during folding. Remarkably, this strategy is fully compatible with glycopeptide synthesis, allowing for the synthesis of homogeneously N79‐glycosylated IL‐15. The effectiveness of RST‐2.0 was further demonstrated through the efficient synthesis of wild‐type and azide‐labeled Interleukin‐2 (IL‐2) analogs. Moreover, the bioactivity of IL‐15 and IL‐2 analogs was validated by CTLL‐2 proliferation assays and microscale thermophoresis (MST). This work provides a de novo synthesis approach to elucidate the role of N‐glycosylation on IL‐15‐mediated immune regulation and lays the foundation for developing next‐generation cancer immunotherapies based on synthetic IL‐15 variants.
Achieving low ON-resistance in E-mode regrown U-shaped p-GaN gate multi-channel HEMT
This work demonstrates an E-mode regrown U-shaped p-GaN gate multi-channel HEMT on a sapphire substrate. The multi-channel access region is favorable to reducing the ON-resistance (RON). E-mode operation was achieved by locally etching through the multiple channels at the gate region and regrowing a p-GaN/AlGaN/GaN gate stack. The currents from multi-channel region merge into the gated channel through the regrown GaN layer. To study the effectiveness of the current merging mechanism, I–V characterization and transmission line method analysis have been conducted. The fabricated device with LGD of 52 μm presents a positive threshold voltage (VTH) of 1.8 V and a low RON of 21.6 Ω mm, corresponding to a specific resistance (RON,SP) of 13.82 mΩ cm2. The resistance of transition region where the multi-channel currents merge into the gated channel is found to account for 34% of the total RON. Temperature-dependent I–V characteristics of the device were investigated. At 150 °C, the percentage of the transition region resistance drops to 11%. The device presents competitive RON–LGD performance among the state-of-the-art GaN devices. These results validate the proposed U-shaped p-GaN gate multi-channel HEMT as a promising approach to reduce the RON of E-mode GaN power devices scaling up (i.e., with larger LGD) for wider operation voltage range.
Textual overlap rather than domain alignment: A comparative study of fine-tuning strategies for specialised machine translation with large language models
General-purpose large language models (LLMs) may struggle in specialised machine translation, but the conditions under which fine-tuning improves translation performance remain unclear. This study compares full-parameter fine-tuning (FPFT) and parameter-efficient fine-tuning (PEFT) for Chinese-English political discourse translation using a purpose-built corpus and the Qwen3-14B model. Translation performance was assessed on three 50-item test sets using BLEU, ROUGE-L F1, METEOR, and BERTScore F1, together with BLEU pass-rate likelihood-ratio G 2 tests, paired t-tests, and paired Cohen’s d z for item-level score differences. The results reveal a clear contrast between unseen in-domain evaluation, maximum-overlap benchmarking, and semantically related but non-fine-tuned evaluation. On Test Set A and Test Set C, neither fine-tuning strategy produced a statistically significant BLEU pass-rate advantage over the base model, and paired tests across the continuous metrics did not show consistent fine-tuning gains. On Test Set B, which was sampled from the fine-tuning corpus, both fine-tuned models substantially outperformed the base model across all four metrics, with FPFT achieving the highest scores and PEFT providing a more computationally efficient alternative. These findings indicate that textual overlap between training and deployment data, rather than broad domain similarity alone, strongly conditions the observed benefit of fine-tuning. The study offers an empirically grounded framework for selecting fine-tuning strategies in specialised machine translation.
Anisotropic NMR as a Crucial Tool for Differentiation of Epimers With High Conformational Flexibility
ABSTRACT Identifying the correct structures of epimers is highly challenging due to the sometimes very subtle differences in their respective NMR signatures. In this context, the analysis of carbon residual chemical shift anisotropies ( 13 C‐RCSAs) and residual dipolar couplings (RDCs) was essential for distinguishing the relative configurations of two tetraprenyltoluquinol epimeric meroterpenoids at C3 ( 1a and 1b ). These compounds feature two remotely located stereoclusters and exhibit significant conformational flexibility. DP4‐based approaches (DP4+ or J ‐DP4) failed to differentiate these epimers. A geometric exploration strategy was developed to investigate the conformational diversity of 1a and 1b while accounting for their inherent flexibility. Then, refining the conformational space and optimizing the fitting of the anisotropic parameters of 1a / 1b measured in a 3 mm semi‐micro compression device using poly‐HEMA gels in DMSO enabled us to discriminate the relative configuration of them.
Robust growth of layered Sn2P2S6 nanoplates with strong in-plane optical anisotropy
Layered ternary metal phosphorous chalcogenides (TMPCs) with low-symmetry structure have emerged as promising candidates for developing high-performance polarization-sensitive optoelectronics and nonlinear optical systems. The production of highly crystalline TMPCs with well-understood optical anisotropy is essential for their device applications. Herein, we report a robust growth of an anisotropic layered TMPC semiconductor Sn2P2S6 via space-confined chemical vapor deposition. The as-grown high-quality Sn2P2S6 nanoplates with uniform edges but different morphologies are identified as a typical semiconductor with a bandgap of 2.12 eV, and their morphology evolution during the growth can be greatly understood by the kinetic Wulff construction theory. The non-centrosymmetric structure of Sn2P2S6 nanoplates enables their strong optical anisotropies, resulting in giant second-harmonic generation anisotropy with the polarized anisotropic ratio up to 38.9. Additionally, they also indicate pronounced in-plane vibration anisotropy, reflecting the directional phonon responses inherent to their lattice symmetry. This work not only offers a robust synthetic strategy for achieving high-quality TMPC crystals but also suggests the large potential of Sn2P2S6 for polarization-sensitive optoelectronic applications.
Pre-transplant dialysis vintage and post-transplant outcomes: A retrospective cohort study in Korean kidney transplant recipients
Background Kidney transplantation (KT) is the preferred treatment for end-stage renal disease (ESRD) due to its advantages over dialysis. Although the benefits of preemptive KT are well established, the association between pre-transplant dialysis duration and post-transplant outcomes remains uncertain. Objective To evaluate the association between pre-transplant dialysis vintage and post-transplant outcomes in Korean KT recipients using real-world data from a tertiary transplant center. Methods We retrospectively evaluated 1,843 first KT recipients transplanted between 2006–2021. Dialysis duration was used as a categorical variable divided by tertiles according to distribution of time of analysis, and preemptive transplantation was categorized as a separate group. Primary outcomes included death-censored graft loss, all-cause mortality and composite outcomes. Survival was assessed using Kaplan–Meier and Cox proportional hazards models at a 95% confidence level. A deceased-donor KT (DDKT) subgroup analysis was also performed. Results 369 patients underwent preemptive KT, and 1,474 dialysis-exposed recipients were categorized into tertile 1 (n = 492), tertile 2 (n = 491), and tertile 3 (n = 491), with mean pre-transplant dialysis durations of 1.2, 21.4, and 107.6 months, respectively. Compared with preemptive KT, all-cause mortality did not differ in the first or second tertiles but was significantly higher in the third tertile (aHR 3.55; 95% CI 1.43–8.81; p = 0.006). In the overall cohort, the third tertile was also associated with higher risks of death-censored graft failure and the composite outcome. However, in the deceased-donor KT subgroup, death-censored graft failure did not differ significantly across tertiles, and the composite outcome did not show a monotonic dose-response pattern. Conclusions Prolonged pre-transplant dialysis was associated with a higher risk of all-cause mortality, whereas its association with graft failure was less consistent, particularly among deceased-donor KT recipients.
High‐Entropy Polymer Electrode for Fast Rechargeable Batteries
ABSTRACT Polymer electrode materials possess the advantages of sustainability, abundant resources, and structural adjustability, yet suffer from poor rate capability and cycling stability. Herein, we propose a concept of molecular structure entropy for the development of a high‐entropy polymer (HEP), wherein molecular structure entropy exerts a significant regulatory effect on the physicochemical and electrochemical performance of the resulting polymer. For sodium‐based batteries, the Na||HEP cell delivers a high reversible capacity of 167.7 mAh g −1 at a current density of 1 A g −1 , a long cycling stability of 5000 cycles, and a high‐rate capability of 111.9 mAh g −1 at a current density of 10 A g −1 , outperforming the low‐entropy polymer. Moreover, the all‐organic battery shows a long stability of 15 000 cycles, corresponding to a continuous running time exceeding 200 days. This work sets a precedent for HEP electrodes and establishes a foundation for their further research.
Three-dimensional high-uniformity magnetic field coils optimized by an IHO algorithm
Highly uniform-magnetic fields play a crucial role in a wide range of quantum systems. In this paper, an improved hippopotamus optimization (IHO) algorithm is introduced to optimize the structure of three-dimensional cylindrical uniform-magnetic field coils. Numerical simulations show that the IHO algorithm achieves higher solution accuracy with fewer iterations than conventional optimization algorithms. Within the proposed coil configuration, the IHO-optimized design can theoretically improve the magnetic field uniformity to the order of 10−10, resulting in improved magnetic field uniformity. We rapidly fabricated the uniform-magnetic field coil model using 3D printing and measured its performance. The measurements show that the magnetic field uniformity reaches the 10−5 level within a central region of approximately 1 cm while remaining on the order of 10−4 over a 2 cm region. These results indicate that the proposed IHO algorithm enables efficient optimization and yields coil designs with improved performance and structural simplicity, thereby offering a practical solution for quantum precision measurement and atomic spin control.
Comparative proteomics and metabolomics reveals distinct host protein quality control and metabolic signatures during recombinant IL1-His and IL15-His expression in Nicotiana benthamiana
Agrobacterium-mediated transient expression in Nicotiana benthamiana is widely used for recombinant biopharmaceutical production. To investigate the host plant response upon human cytokine production with contrast accumulation, we expressed codon optimized human IL1 beta, serving as a high expression benchmark with a yield of approximately 80 μg/g leaf fresh weight, and IL15 with undetected signal on western blot, representing protein with low level of accumulation, using the geminiviral vector system. A combined proteomics and metabolomics technique was applied to elucidate underlying cellular mechanisms. Quantitative proteomics revealed that IL1-His was robustly detected (9 unique peptides, 83% coverage), whereas no IL15-His–derived peptides were identified. Based on pathway analysis, the expression of IL15-His induced chaperone expression, with downregulation of photosynthetic and primary metabolism pathways. Additionally, metabolomic pathway analysis revealed that IL1-His preferentially drives the branched chain amino acid biosynthesis, but IL15-His shifts metabolism towards phenylpropanoid biosynthesis routes. These findings underscore that the characteristics of the target protein and its interaction with the host's physiology could influence the yield of the recombinant protein production in plants.
Nickel–Boryl‐Catalyzed Modular Alkyl Difluoromethylation Enabled by an NMP‐Stabilized ICF <sub>2</sub> H Reagent
ABSTRACT The difluoromethyl (CF 2 H) moiety is a privileged pharmacophore that imparts enhanced metabolic stability, lipophilicity, and bioisosteric properties to drug candidates. While aryl difluoromethylation methods are well‐established, catalytic approaches for constructing C( sp 3 )─CF 2 H bonds remain underdeveloped. Herein, we introduce a nickel/boron‐cooperative catalytic system for the cross‐electrophile difluoromethylation of diverse alkyl halides, as well as hydrodifluoromethylation of unactivated alkenes, utilizing difluoroiodomethane (CF 2 HI) stabilized as a liquid reagent through hydrogen‐bonding interaction with N‐methylpyrrolidone (NMP). This stabilization enables high‐concentration handling and overcomes volatility and solubility issues. The mild protocol exhibits excellent functional group tolerance, accommodates complex heterocycles, and facilitates late‐stage modification of bioactive compounds. Mechanistic investigations reveal a radical pathway mediated by Ni(I/II/III) intermediates. This versatile platform expands access to CF 2 H‐containing scaffolds for medicinal chemistry applications.
Integrating single-crystal LiNbO3 thin film on diamond for high-frequency surface acoustic wave devices
The continuous performance leap of surface acoustic wave (SAW) devices is primarily driven by the evolution of piezoelectric-on-insulator substrates. Featuring exceptional acoustic velocity and thermal conductivity, diamond has emerged as a highly promising successor to existing Si and SiC supporting substrates. In this Letter, we successfully fabricate single-crystal LiNbO3-on-diamond (LNOD) substrates via micro-transfer printing (MTP). This approach circumvents the thermal expansion coefficient mismatch inherent to ion slicing and ensures the superior single-crystallinity that is unattainable via heteroepitaxial growth. The LNOD substrates exhibit an intimate heterointerface, a smooth surface, and excellent crystallinity of thin-film LiNbO3 with a rocking curve full-width at half-maximum of 0.037°. Furthermore, shear horizontal mode SAW resonators operating at 5 GHz on LNOD substrates are demonstrated, marking the first reported responses of SAW resonators on this platform. These results significantly outperform prior works, validating the MTP-fabricated LNOD substrates as promising candidates for future high-performance radio frequency acoustic devices.
Population structure and diversity of common bean (Phaseolus vulgaris L.) landraces in the Peruvian Amazon
Common bean ( Phaseolus vulgaris L.) is a globally important grain legume, yet the genetic diversity of landraces from the Peruvian Amazon remains poorly characterized. This study aimed to assess the population structure and genetic diversity of Amazonian common bean by integrating morphological and genome-wide SNP data. A total of 476 accessions were phenotyped using 18 morphological traits, and 647 accessions were genotyped with 23,050 high-quality DArTseq SNP markers. Cluster and population structure analyses consistently identified two major genetic groups corresponding to the Andean (n = 284) and Mesoamerican (n = 363) gene pools, with further subdivision into four subgroups at K = 4. Principal Coordinate Analysis supported this structure, with the first axis explaining 62.62% of the variation in the molecular data. Genetic diversity was high, with 94.9% of SNPs successfully mapped and more than 94% of loci polymorphic in both groups. However, observed heterozygosity was low (Ho = 0.035–0.041) compared to expected heterozygosity (He ≈ 0.147–0.148), and inbreeding coefficients were high (FIS = 0.52–0.54), consistent with the predominantly self-pollinating mating system. Hill number analyses indicated similar allelic richness between groups (q = 0: α ≈ 1.95–1.97) and low differentiation in allele presence (β = 1.04), whereas differentiation increased when allele frequencies were considered (q = 2: β ≈ 1.4–1.5). Morphological analyses revealed substantial phenotypic variation, including flowering time (32–75 days), pod length (6.5–17.3 cm), and number of locules per pod (2–11), and identified four distinct phenotypic clusters. No redundant accessions were detected. These results indicate that Amazonian landraces harbor high levels of genetic and phenotypic diversity structured by gene pool origin and local adaptation. The integration of morphological and SNP data provides a robust framework for germplasm characterization and highlights the importance of conserving these genetic resources for future breeding and sustainable agriculture.
Organometallic Frameworks for Efficient Electrocatalytic CO <sub>2</sub> Reduction Reactions
ABSTRACT The electrocatalytic conversion of CO 2 to value‐added chemicals driven by renewable electricity offers a viable strategy to reduce atmospheric CO 2 concentration and realize energy storage. Crystalline porous metal‐organic frameworks (MOFs) with periodically ordered isolated metal active sites and large surface areas represent promising CO 2 reduction reaction (CO 2 RR) catalysts due to their rapid CO 2 adsorption kinetics. However, conventional MOFs typically exhibit insufficient CO 2 RR current densities stemming from inherent low electrical conductivity and sluggish electron transfer kinetics. Introducing Metal‐C bonds into the framework can directly regulate the electronic structure of the metal center, optimizing intermediate adsorption. Herein, we synthesized two organometallic frameworks featuring carbon‐silver connectivity to enhance the CO 2 RR performances. The distinctive σ‐π coordination motif between alkyne moieties and metal centers endows these frameworks with enhanced electron transfer capability, superior CO 2 activation ability, and significantly improved CO 2 RR performance. Crucially, these materials achieve exceptional CO Faraday efficiencies (FE CO ) exceeding 90% when operated at industrially relevant current densities (> 500 mA cm −2 ), surpassing most reported MOF‐based systems. This work establishes a novel design paradigm for organometallic frameworks and accelerates their practical deployment in industrial CO 2 electroreduction processes.
Spin-reorientation-triggered non-monotonic low-temperature coercivity and voltage-gated two-stage hydrogenation in PrCo5
The spin-reorientation transition (SRT) in rare-earth permanent magnets often reconfigures magnetic anisotropy, yet its direct impact on low-temperature coercivity remains underexplored. In this work, we report a non-monotonic temperature dependence of coercivity in PrCo5, governed by an SRT at 107 K that switches the easy magnetization direction from uniaxial to easy-cone. Such behavior is attributed to competing Pr 4f and Co 3d sublattice anisotropies, which are absent in non-SRT SmCo5. Voltage-controlled hydrogen ion insertion was then employed as a continuous, controllable, and mild tuning strategy to harness this behavior, enabling a two-stage modulation of both coercivity and SRT. These findings not only establish ion insertion as an effective approach for mapping and programming spin-reorientation-driven anisotropy landscapes but also highlight the promise of PrCo5 as a tunable functional material for designing adaptive magnetic memory devices under cryogenic conditions.
Incidence and risk factors for recurrent IgA nephropathy after kidney transplantation: A multicenter cohort study from Denmark
Background Recurrent immunoglobulin A nephropathy after kidney transplantation remains a major clinical challenge, but risk factors are not fully defined. This study aimed to evaluate the incidence of biopsy-proven recurrent IgAN and identify risk factors for recurrence in a contemporary Scandinavian cohort. Methods We conducted a multicenter cohort study including adult patients with biopsy-proven immunoglobulin A nephropathy who received a first kidney-only transplantation between 1990 and 2020 across two Danish transplantation centers. Recurrence incidence and associations with clinical and donor-related characteristics were assessed during follow-up. Results A total of 118 recipients were followed for a median of 5.5 years. Biopsy-confirmed recurrence occurred in 14% of patients, corresponding to a cumulative incidence of 16% at 10 years post-transplantation. Younger age at immunoglobulin A nephropathy diagnosis, faster progression to kidney failure, and receipt of a kidney from a living or genetically related donor were independently associated with an increased risk of recurrence. Maintenance post-transplant steroid use was not associated with recurrence. Recurrent immunoglobulin A nephropathy was associated with an increased risk of graft failure compared with non-recurrent disease (unadjusted HR 3.8; adjusted HR 6.7). Conclusions Recurrence of IgAN after kidney transplantation remains a clinically significant challenge, associated with younger age, rapid progression to KF, and transplantation from living or genetically related donors. Maintenance post-transplant steroid use was not associated with recurrence risk in this cohort. Larger and more diverse cohorts are warranted to clarify donor-related risk, strengthen the evidence on immunosuppressive protocols and guide strategies to improve graft outcomes.
Fluorogenic Coupled Assays Reveal Catalytic Properties, Inhibition Constants and Cellular Location of Mucin‐Active Carbohydrate Sulfatases
ABSTRACT Sulfated glycans play a central role in human health and influence cell signaling, cancer progression, pathogen invasion, and host‐microbiome interactions. Metabolism of these glycans requires a specialized class of enzymes termed carbohydrate sulfatases. These enzymes are particularly important in the human gut where sulfated colonic mucin is produced and subsequently degraded by colonic bacteria. Despite the biological importance of carbohydrate sulfatases, there is currently a lack of chemical tools to study their activity, substrate selectivity, inhibition, and the discovery of novel enzymes. To address this, we have synthesized new chemical tools to rapidly and quantitatively determine the activity and selectivity of carbohydrate sulfatases in plate‐based coupled assays. We have synthesized 3‐ O ‐sulfated fluorogenic glycosides using efficient synthetic routes and combined these fluorogenic substrates with a glycosidase that selectively cleaves unsulfated glycosides, allowing sensitive detection of sulfatase activity on both purified protein and cell lysate from the S1_20 subfamily sulfatases. Furthermore, we show that the assay enables differentiation and quantification of substrate specificity, identification of sulfatase inhibitors, and determination of sulfatase (sub‐)cellular location for two S1_20 subfamily sulfatases. Collectively, we anticipate that these tools will further our understanding of the interplay between carbohydrate sulfatases, sulfated glycans, and human health.