Pushing Theoretical Potassium Storage Limits of MXenes through Introducing New Carbon Active Sites.

Surface-driven capacitive storage enhances rate performance and cyclability, thereby improving the efficacy of high-power electrode materials and fast-charging batteries. Conventional defect engineering, widely-employed capacitive storage optimization strategy, primarily focuses on the influence of defects themselves on capacitive behaviors. However, the role of local environment surrounding defects, which significantly affects surface properties, remains largely unexplored for lack of suitable material platform and has long been neglected. As proof-of-concept, typical Ti3C2Tx MXenes are chosen as model materials owing to metallic conductivity and tunable surface properties, satisfying the requirements for capacitive-type electrodes. Using density functional theory (DFT) calculations, the potential of MXenes with modulated local atomic environment is anticipated and introducing new carbon sites found near pores can activate electrochemically inert surface, attaining record theoretical potassium storage capacities of MXenes (291 mAh g-1). This supposition is realized through atomic tailoring via chemical scissor within sublayers, exposing new sp3-hybridized carbon active sites. The resulting MXenes demonstrate unprecedented rate performance and cycling stability. Notably, MXenes with higher carbon exposure exhibit a record-breaking capacity over 200 mAh g-1 and sustain a capacity retention higher than 80% after 20 months. These findings underscore the effectiveness of regulating defects' neighboring environment and illuminate future high-performance electrode design.

A dynamic framework for contractors to measure the performance of highway maintenance based on grey theory.

Highway maintenance performance measurement is the key to implementing performance-based contracting (PBC). However, contractors have struggled with accurately understanding client intent and translating performance goals into measurable indicators. To make PBC successfully applied, this study proposes a dynamic performance measurement framework of highway routine maintenance based on grey theory. A performance indicator system is established based on the organizational structure of highway assets and the bill of quantities in the real world. In addition, a statistical analysis using the data about maintenance cost and highway condition score has been conducted to ascertain the weights and thresholds assigned to various indicators. As a result, the performance indicators, their corresponding weights, and thresholds can be flexibly adjusted to accommodate diverse periods and areas. Then, the grey theory has been employed to evaluate the comprehensive performance level of service within a region. This framework is experimented with using the data of three maintenance areas in Shaanxi Province, China: Qiaogouwan, Huaziping, and Ansai. At the end of the process, comparison and sensitivity analysis are conducted. The results demonstrate the model's reasonability and robustness, providing valuable tools for contractors to assess the performance of highway maintenance in meeting client specifications.

Hyaluronic acid-coated polypeptide nanogel enhances specific distribution and therapy of tacrolimus in rheumatoid arthritis.

Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels' disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.

UBE3C restricts EV-A71 replication by ubiquitination-dependent degradation of 2C.

Ubiquitin modification of viral proteins to degrade or regulate their function is one of the strategies of the host to resist viral infection. Here, we report that ubiquitin protein ligase E3C (UBE3C), an E3 ubiquitin ligase, displayed inhibitory effects on EV-A71 replication. UBE3C knockdown resulted in increased viral protein levels and virus titers, whereas overexpression of UBE3C reduced EV-A71 replication. To explore the mechanism by which UBE3C affected EV-A71 infection, we found that the C-terminal of UBE3C bound to 2C protein and facilitated K33/K48-linked ubiquitination degradation of 2C K268. Moreover, UBE3C lost its ability to degrade 2C K268R and had a diminished inhibitory impact against the replication of recombinant EV-A71-FY-2C K268R. In addition, UBE3C also promoted ubiquitination degradation of the 2C protein of CVB3 and CVA16 and inhibited viral replication. Thus, our findings reveal a novel mechanism that UBE3C acts as an enterovirus host restriction factor, including EV-A71, by targeting the 2C protein. IMPORTANCE: The highly conserved 2C protein of EV-A71 is a multifunctional protein and plays a key role in the replication cycle. In this study, we demonstrated for the first time that UBE3C promoted the degradation of 2C K268 via K33/K48-linked ubiquitination, thereby inhibiting viral proliferation. Our findings advance the knowledge related to the roles of 2C in EV-A71 virulence and the ubiquitination pathway in the host restriction of EV-A71 infection.

Selectively T cell phosphorylation activation of azvudine in the thymus tissue with immune protection effect.

Thymus is the important immune organ, responsible for T cell development and differentiation. The lower circulating T counts have been observed in patients who died from COVID-19 compared with survivors. Azvudine, also known as FNC, is a thymus-homing anti-SARS-CoV-2 drug in treating COVID-19 patients. In this study, single-cell transcriptome, proteomics, and parallel reaction monitoring (PRM) were applied to insight into the activation process of FNC in rat and SARS-CoV-2 rhesus monkey thymus. The results indicated that thymic immune cells possess a robust metabolic capacity for cytidine-analogue drugs such as FNC. Key enzymes involved in the FNC phosphorylation process, such as Dck, Cmpk1, and Nme2, were highly expressed in CD4+ T cells, CD8+ T cells, and DP (CD4+ CD8+) cells. Additionally, FNC could upregulate multiple phosphorylated kinases in various cell types while downregulating the phosphatases, phosphoribosyl transferases, and deaminases, respectively. The robust phosphorylation capacity of the thymus for cytidine analogue drug FNC, and the activation effect of FNC on the NAs metabolism system potentially contribute to its enrichment in the thymus and immune protection effect. This suggests that it is crucial to consider the expression level of phosphorylation kinases when evaluating NA drug properties, as an important factor during antiviral drug design.

Bioactive prenylated c6-c3 derivatives from the roots of Illicium brevistylum.

Three new prenylated C6-C3 compounds (1-3), together with two known prenylated C6-C3 compounds (4-5) and one known C6-C3 derivative (6), were isolated from the roots of Illicium brevistylum A. C. Smith. The structures of 1-3 were elucidated by spectroscopic methods including 1D and 2D NMR, HRESIMS, CD experiments and ECD calculations. The structure of illibrefunone A (1) was confirmed by single-crystal X-ray diffraction analysis. All compounds were evaluated in terms of their anti-inflammatory potential on nitric oxide (NO) generation in lipopolysaccharide-stimulated murine RAW264.7 macrophages and murine BV2 microglial cells, antiviral activity against Coxsackievirus B3 (CVB3) and influenza virus A/Hanfang/359/95 (H3N2). Compounds 3 and 4 exhibited potent inhibitory effects on the production of NO in RAW 264.7 cells with IC50 values of 20.57 and 12.87 µM respectively, which were greater than those of dexamethasone (positive control). Compounds 1 and 4-6 exhibited weak activity against Coxsackievirus B3, with IC50 values ranging from 25.87 to 33.33 µM.

Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer's disease.

Communication between glial cells has a profound impact on the pathophysiology of Alzheimer's disease (AD). We reveal here that reactive astrocytes control cell distancing in peri-plaque glial nets, which restricts microglial access to amyloid deposits. This process is governed by guidance receptor Plexin-B1 (PLXNB1), a network hub gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes. Plexin-B1 deletion in a mouse AD model led to reduced number of reactive astrocytes and microglia in peri-plaque glial nets, but higher coverage of plaques by glial processes, along with transcriptional changes signifying reduced neuroinflammation. Additionally, a reduced footprint of glial nets was associated with overall lower plaque burden, a shift toward dense-core-type plaques and reduced neuritic dystrophy. Altogether, our study demonstrates that Plexin-B1 regulates peri-plaque glial net activation in AD. Relaxing glial spacing by targeting guidance receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD.

Remediation of Metal Oxide Nanotoxicity with a Functional Amyloid.

Understanding the environmental health and safety of nanomaterials (NanoEHS) is essential for the sustained development of nanotechnology. Although extensive research over the past two decades has elucidated the phenomena, mechanisms, and implications of nanomaterials in cellular and organismal models, the active remediation of the adverse biological and environmental effects of nanomaterials remains largely unexplored. Inspired by recent developments in functional amyloids for biomedical and environmental engineering, this work shows their new utility as metallothionein mimics in the strategically important area of NanoEHS. Specifically, metal ions released from CuO and ZnO nanoparticles are sequestered through cysteine coordination and electrostatic interactions with beta-lactoglobulin (bLg) amyloid, as revealed by inductively coupled plasma mass spectrometry and molecular dynamics simulations. The toxicity of the metal oxide nanoparticles is subsequently mitigated by functional amyloids, as validated by cell viability and apoptosis assays in vitro and murine survival and biomarker assays in vivo. As bLg amyloid fibrils can be readily produced from whey in large quantities at a low cost, the study offers a crucial strategy for remediating the biological and environmental footprints of transition metal oxide nanomaterials.

Controlling nanoparticle-induced endothelial leakiness with the protein corona.

Understanding nanoparticle-cell interaction is essential for advancing research in nanomedicine and nanotoxicology. Apart from the transcytotic pathway mediated by cellular recognition and energetics, nanoparticles (including nanomedicines) may harness the paracellular route for their transport by inducing endothelial leakiness at cadherin junctions. This phenomenon, termed as NanoEL, is correlated with the physicochemical properties of the nanoparticles in close association with cellular signalling, membrane mechanics, as well as cytoskeletal remodelling. However, nanoparticles in biological systems are transformed by the ubiquitous protein corona and yet the potential effect of the protein corona on NanoEL remains unclear. Using confocal fluorescence microscopy, biolayer interferometry, transwell, toxicity, and molecular inhibition assays, complemented by molecular docking, here we reveal the minimal to significant effects of the anionic human serum albumin and fibrinogen, the charge neutral immunoglobulin G as well as the cationic lysozyme on negating gold nanoparticle-induced endothelial leakiness in vitro and in vivo. This study suggests that nanoparticle-cadherin interaction and hence the extent of NanoEL may be partially controlled by pre-exposing the nanoparticles to plasma proteins of specific charge and topology to facilitate their biomedical applications.

Regulating Local Atomic Environment around Vacancies for Efficient Hydrogen Evolution.

Defect engineering is essential for the development of efficient electrocatalysts at the atomic level. While most work has focused on various vacancies as effective catalytic modulators, little attention has been paid to the relation between the local atomic environment of vacancies and catalytic activities. To face this challenge, we report a facile synthetic approach to manipulate the local atomic environments of vacancies in MoS2 with tunable Mo-to-S ratios. Our studies indicate that the MoS2 with more Mo terminated vacancies exhibits better hydrogen evolution reaction (HER) performance than MoS2 with S terminated vacancies and defect-free MoS2. The improved performance originates from the adjustable orbital orientation and distribution, which is beneficial for regulating H adsorption and eventually boosting the intrinsic per-site activity. This work uncovers the underlying essence of the local atomic environment of vacancies on catalysis and provides a significant extension of defect engineering for the rational design of transition metal dichalcogenides (TMDs) catalysts and beyond.

Identification of dihydroquinolizinone derivatives with nitrogen heterocycle moieties as new anti-HBV agents.

The sustained loss of HBsAg is considered a pivotal indicator for achieving functional cure of HBV. Dihydroquinolizinone derivatives (DHQs) have demonstrated remarkable inhibitory activity against HBsAg both in vitro and in vivo. However, the reported neurotoxicity associated with RG7834 has raised concerns regarding the development of DHQs. In this study, we designed and synthesized a series of DHQs incorporating nitrogen heterocycle moieties. Almost all of these compounds exhibited potent inhibition activity against HBsAg, with IC50 values at the nanomolar level. Impressively, the compound (S)-2a (10 µM) demonstrated a comparatively reduced impact on the neurite outgrowth of HT22 cells and isolated mouse DRG neurons in comparison to RG7834, thereby indicating a decrease in neurotoxicity. Furthermore, (S)-2a exhibited higher drug exposures than RG7834. The potent anti-HBV activity, reduced neurotoxicity, and favorable pharmacokinetic profiles underscore its promising potential as a lead compound for future anti-HBV drug discovery.

Aptamers: Promising Reagents in Biomedicine Application.

Nucleic acid aptamers, often termed "chemical antibodies," are short, single-stranded DNA or RNA molecules, which are selected by SELEX. In addition to their high specificity and affinity comparable to traditional antibodies, aptamers have numerous unique advantages such as wider identification of targets, none or low batch-to-batch variations, versatile chemical modifications, rapid mass production, and lack of immunogenicity. These characteristics make aptamers a promising recognition probe for scientific research or even clinical application. Aptamer-functionalized nanomaterials are now emerged as a promising drug delivery system for various diseases with decreased side-effects and improved efficacy. In this review, the technological strategies for generating high-affinity and biostable aptamers are introduced. Moreover, the development of aptamers for their application in biomedicine including aptamer-based biosensors, aptamer-drug conjugates and aptamer functionalized nanomaterials is comprehensively summarized.

Role of Alkyl Chain Length in Surfactant-Induced Precipitation of Reactive Brilliant Blue KN-R.

To develop a cost-effective method for the effective removal of reactive brilliant blue KN-R (RBB KN-R) from wastewater, we investigated the interactions between RBB KN-R and three cationic surfactants with different alkyl chain lengths, namely dodecyltrimethylammonium bromide (DTAB), tetradecyltrimethylammonium bromide (TTAB), and cetyltrimethylammonium bromide (CTAB). Employing a conductivity analysis, surface tension analysis, ultraviolet-visible spectrophotometry, and molecular dynamics simulation, we ascertained that RBB KN-R formed a 1:1 molar ratio dye-surfactant complex with each surfactant through electrostatic attraction. Notably, an augmentation in alkyl chain length correlated with increased binding strength between RBB KN-R and the surfactant. The resulting dye-surfactant complex exhibited heightened surface activity, enabling interactions through hydrophobic forces to generate dye-surfactant aggregates when the molar ratio was below 1:1. Within these mixed aggregates, self-assembly of RBB KN-R molecules occurred, leading to the formation of dye aggregates. Due to the improved hydrophobicity with increased alkyl chain length, TTAB and CTAB could encapsulate dye aggregates within the mixed aggregates, but DTAB could not. The RBB KN-R aggregates tended to distribute on the surface of the RBB KN-R-DTAB mixed aggregates, resulting in low stability. Thus, at a DTAB concentration lower than CMC, insoluble particles readily formed and separated from surfactant aggregates at an RBB KN-R and DTAB molar ratio of 1:4. Analyzing the RBB KN-R precipitate through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) and measuring the DTAB concentration in the supernate revealed that, at this molar ratio, all RBB KN-R precipitated from the dye-surfactant mixed solution, with only 7.5 ± 0.5% of DTAB present in the precipitate. Furthermore, the removal ratio of RBB KN-R reached nearly 100% within a pH range of 1.0 to 9.0 and standing time of 6 h. The salt type and concentration did not significantly affect the precipitation process. Therefore, this simultaneous achievement of successful RBB KN-R removal and effective separation from DTAB underscores the efficacy of the proposed approach.

Musashi-2 potentiates colorectal cancer immune infiltration by regulating the post-translational modifications of HMGB1 to promote DCs maturation and migration.

Post-translational modifications (PTMs) of the non-histone protein high-mobility group protein B1 (HMGB1) are involved in modulating inflammation and immune responses. Recent studies have implicated that the RNA-binding protein (RBP) Musashi-2 (MSI2) regulates multiple critical biological metabolic and immunoregulatory functions. However, the precise role of MSI2 in regulating PTMs and tumor immunity in colorectal cancer (CRC) remains unclear. Here, we present data indicating that MSI2 potentiates CRC immunopathology in colitis-associated colon cancer (CAC) mouse models, cell lines and clinical specimens, specifically via HMGB1-mediated dendritic cell (DC) maturation and migration, further contributes to the infiltration of CD4+ and CD8+ T cells and inflammatory responses. Under stress conditions, MSI2 can exacerbate the production, nucleocytoplasmic transport and extracellular release of damage-associated molecular patterns (DAMPs)-HMGB1 in CRC cells. Mechanistically, MSI2 mainly enhances the disulfide HMGB1 production and protein translation via direct binding to nucleotides 1403-1409 in the HMGB1 3' UTR, and interacts with the cytoplasmic acetyltransferase P300 to upregulate its expression, further promoting the acetylation of K29 residue in HMGB1, thus leading to K29-HMGB1 nucleocytoplasmic translocation and extracellular release. Furthermore, blocking HMGB1 activity with glycyrrhizic acid (Gly) attenuates MSI2-mediated immunopathology and immune infiltration in CRC in vitro and in vivo. Collectively, this study suggests that MSI2 may improve the prognosis of CRC patients by reprogramming the tumor immune microenvironment (TIME) through HMGB1-mediated PTMs, which might be a novel therapeutic option for CRC immunotherapy.

Dynamically Reconstructed Triple-Copper-Vacancy Associates Confined in Cu Nanowires Enabling High-Rate and Selective CO2 Electroreduction to C2+ Products.

Electrochemically reconstructed Cu-based catalysts always exhibit enhanced CO2 electroreduction performance; however, it still remains ambiguous whether the reconstructed Cu vacancies have a substantial impact on CO2-to-C2+ reactivity. Herein, Cu vacancies are first constructed through electrochemical reduction of Cu-based nanowires, in which high-angle annular dark-field scanning transmission electron microscopy image manifests the formation of triple-copper-vacancy associates with different concentrations, confirmed by positron annihilation lifetime spectroscopy. In situ attenuated total reflection-surface enhanced infrared absorption spectroscopy discloses the triple-copper-vacancy associates favor *CO adsorption and fast *CO dimerization. Moreover, density-functional-theory calculations unravel the triple-copper-vacancy associates endow the nearby Cu sites with enriched and disparate local charge density, which enhances the *CO adsorption and reduces the CO-CO coupling barrier, affirmed by the decreased *CO dimerization energy barrier by 0.4 eV. As a result, the triple-copper-vacancy associates confined in Cu nanowires achieve a high Faradaic efficiency of over 80% for C2+ products in a wide current density range of 400-800 mA cm-2, outperforming most reported Cu-based electrocatalysts.

STAMENLESS1 activates SUPERWOMAN 1 and FLORAL ORGAN NUMBER 1 to control floral organ identities and meristem fate in rice.

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.

Tribbles pseudokinase 3 promotes enterovirus A71 infection via dual mechanisms.

Enterovirus A71 (EV-A71) is the main pathogen causing hand, foot and mouth disease (HFMD) in children and occasionally associated with neurological diseases such as aseptic meningitis, brainstem encephalitis (BE) and acute flaccid paralysis. We report here that cellular pseudokinase tribbles 3 (TRIB3) facilitates the infection of EV-A71 via dual mechanisms. In one hand, TRIB3 maintains the metabolic stability of scavenger receptor class B member 2 (SCARB2), the bona fide receptor of EV-A71, to enhance the infectious entry and spreading of the virus. On the other hand, TRIB3 facilitates the replication of EV-A71 RNA in a SCARB2-independent manner. The critical role of TRIB3 in EV-A71 infection and pathogenesis was further demonstrated in vivo in mice. In comparison to wild-type C57BL/6 mice, EV-A71 infection in TRIB3 knockdown mice (Trib3+/-) resulted in significantly lower viral loads in muscular tissues and reduced lethality and severity of clinical scores and tissue pathology. In addition, TRIB3 also promoted the replication of coxsackievirus B3 (CVB3) and coxsackievirus A16 (CVA16) in vitro. In conclusion, our results suggest that TRIB3 is one of key host cellular proteins required for the infection and pathogenesis of EV-A71 and some other human enteroviruses and may thus be a potential therapeutic target for combating the infection of those viruses.

Endothelial leakiness elicited by amyloid protein aggregation.

Alzheimer's disease (AD) is a major cause of dementia debilitating the global ageing population. Current understanding of the AD pathophysiology implicates the aggregation of amyloid beta (Aß) as causative to neurodegeneration, with tauopathies, apolipoprotein E and neuroinflammation considered as other major culprits. Curiously, vascular endothelial barrier dysfunction is strongly associated with Aß deposition and 80-90% AD subjects also experience cerebral amyloid angiopathy. Here we show amyloid protein-induced endothelial leakiness (APEL) in human microvascular endothelial monolayers as well as in mouse cerebral vasculature. Using signaling pathway assays and discrete molecular dynamics, we revealed that the angiopathy first arose from a disruption to vascular endothelial (VE)-cadherin junctions exposed to the nanoparticulates of Aß oligomers and seeds, preceding the earlier implicated proinflammatory and pro-oxidative stressors to endothelial leakiness. These findings were analogous to nanomaterials-induced endothelial leakiness (NanoEL), a major phenomenon in nanomedicine depicting the paracellular transport of anionic inorganic nanoparticles in the vasculature. As APEL also occurred in vitro with the oligomers and seeds of alpha synuclein, this study proposes a paradigm for elucidating the vascular permeation, systemic spread, and cross-seeding of amyloid proteins that underlie the pathogeneses of AD and Parkinson's disease.

Assessing management practices for variants of uncertain significance among genetic counselors in pediatrics.

Increased utilization of genomic sequencing in pediatric medicine has increased the detection of variants of uncertain significance (VUS). Periodic VUS reinterpretation can clarify clinical significance and increase diagnostic yield, highlighting the importance of systematic VUS tracking and reinterpretation. There are currently no standardized guidelines or established best practices for VUS management, and our understanding of how genetic counselors (GCs) track and manage VUS results for pediatric patients is limited. In this exploratory study, GCs in pediatric clinics in North America were surveyed about their VUS management practices. A total of 124 responses were included in the analysis. The majority (n = 115, 92.7%) of GCs reported that VUS management workflows were at the discretion of each individual provider in their workplace. Approximately half (n = 65, 52%) kept track of patient VUS results over time, and GCs with lower patient volumes were more likely to do so (p = 0.04). While 95% (n = 114) of GCs had requested VUS reinterpretation at least once, only 5% (n = 6) requested it routinely. Most (n = 80, 86%) GCs notified patients when a VUS was reclassified, although methods of recontact differed when the reclassification was an upgrade versus a downgrade. GCs who asked patients to stay in touch through periodic recontact or follow-up appointments were more likely to request VUS reinterpretation (p = 0.01). The most frequently reported barriers to requesting reinterpretation regularly were patients being lost to follow-up (n = 39, 33.1%), insufficient bandwidth (n = 27, 22.9%), and lack of standardized guidelines (n = 25, 21.2%). GCs had consistent overall practices around VUS management around investigation, disclosure, reinterpretation, and recontact, but specific methods used differed and were at the discretion of each provider. These results showcase the current landscape of VUS management workflows in pediatrics and the challenges associated with adopting more uniform practices. The study findings can help inform future strategies to develop standardized guidelines surrounding VUS management.

Cadinane sesquiterpenes from the stems and branches of Illicium ternstroemioides.

Three new cadinane sesquiterpenes (1-3) and three known sesquiterpenes were isolated from the stems and branches of Illicium ternstroemioides A. C. Smith. The structures of the new compounds were elucidated by extensive analysis of spectroscopic and HRESIMS data. The structures of illiternins A-C (1-3) were confirmed by single crystal X-ray diffraction, allowing for the determination of their absolute configurations. Compounds 3 and 6 exhibited antiviral activity against Coxsackievirus B3 with IC50 values of 33.3 and 57.7 µM, respectively.