Acute stress during witnessing injustice shifts third-party interventions from punishing the perpetrator to helping the victim.

People tend to intervene in others' injustices by either punishing the transgressor or helping the victim. Injustice events often occur under stressful circumstances. However, how acute stress affects a third party's intervention in injustice events remains open. Here, we show a stress-induced shift in third parties' willingness to engage in help instead of punishment by acting on emotional salience and central-executive and theory-of-mind networks. Acute stress decreased the third party's willingness to punish the violator and the severity of the punishment and increased their willingness to help the victim. Computational modeling revealed a shift in preference of justice recovery from punishment the offender toward help the victim under stress. This finding is consistent with the increased dorsolateral prefrontal engagement observed with higher amygdala activity and greater connectivity with the ventromedial prefrontal cortex in the stress group. A brain connectivity theory-of-mind network predicted stress-induced justice recovery in punishment. Our findings suggest a neurocomputational mechanism of how acute stress reshapes third parties' decisions by reallocating neural resources in emotional, executive, and mentalizing networks to inhibit punishment bias and decrease punishment severity.

Evolutionary pathways to SARS-CoV-2 resistance are opened and closed by epistasis acting on ACE2.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects a broader range of mammalian species than previously predicted, binding a diversity of angiotensin converting enzyme 2 (ACE2) orthologs despite extensive sequence divergence. Within this sequence degeneracy, we identify a rare sequence combination capable of conferring SARS-CoV-2 resistance. We demonstrate that this sequence was likely unattainable during human evolution due to deleterious effects on ACE2 carboxypeptidase activity, which has vasodilatory and cardioprotective functions in vivo. Across the 25 ACE2 sites implicated in viral binding, we identify 6 amino acid substitutions unique to mouse-one of the only known mammalian species resistant to SARS-CoV-2. Substituting human variants at these positions is sufficient to confer binding of the SARS-CoV-2 S protein to mouse ACE2, facilitating cellular infection. Conversely, substituting mouse variants into either human or dog ACE2 abolishes viral binding, diminishing cellular infection. However, these same substitutions decrease human ACE2 activity by 50% and are predicted as pathogenic, consistent with the extreme rarity of human polymorphisms at these sites. This trade-off can be avoided, however, depending on genetic background; if substituted simultaneously, these same mutations have no deleterious effect on dog ACE2 nor that of the rodent ancestor estimated to exist 70 million years ago. This genetic contingency (epistasis) may have therefore opened the road to resistance for some species, while making humans susceptible to viruses that use these ACE2 surfaces for binding, as does SARS-CoV-2.

Occurrence and Flow Behavior for Oil Transport in Mixed Wetting Nanoscale Shale Bedding Fractures.

Shale reservoirs are characterized by an abundance of nanoscale porosities and microfractures. The states of fluid occurrence and flow behaviors within nanoconfined spaces necessitate novel research approaches, as traditional percolation mathematical models are inadequate for accurately depicting these phenomena. This study takes the Gulong shale reservoir in China as the subject of its research. Initially, the unique mixed wetting characteristics of the Gulong shale reservoir are examined and characterized using actual micropore images. Subsequently, the occurrence and flow behavior of oil within the nanoscale bedding fractures under various wettability scenarios are described through a combination of microscopic pore image and molecular dynamics simulations. Ultimately, a mathematical model is established that depicts the velocity distribution of oil and its apparent permeability. This study findings indicate that when the scale of the shale bedding fractures is less than 100 nm, the impact of the nanoconfinement effect is significant and cannot be overlooked. In this scenario, the state of oil occurrence and its flow behavior are influenced by the initial oil-wet surface area on the mixed wetting walls. The study quantifies the velocity and density distribution of oil in mixed wetting nanoscale shale bedding fractures through a mathematical model, providing a crucial theoretical basis for upscaling from the nanoscale to the macroscale.

Prominent Intrinsic Proton Conduction in Two Robust Zr/Hf Metal-Organic Frameworks Assembled by Bithiophene Dicarboxylate.

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3-b]thiophene-2,5-dicarboxylic acid (H2DTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [Zr6O4(OH)4(DTD)6]·5DMF·H2O (Zr-DTD) and [Hf6O4(OH)4(DTD)6]·4DMF·H2O (Hf-DTD), using solvothermal means. The presence of Zr6 or Hf6 nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water. Their proton conductivity was fully examined at various relative humidities (RHs) and temperatures. Creating intricate and rich H-bonded networks between the guest water molecules, coordination solvent molecules, thiophene-S, -COOH, and -OH units within the framework assisted proton transfer. As a result, both MOFs manifest the maximum proton conductivity of 0.67 × 10-2 and 4.85 × 10-3 S·cm-1 under 98% RH/100 °C, making them the top-performing proton-conductive Zr/Hf-MOFs. Finally, by combining structural characteristics and activation energies, potential proton conduction pathways for the two MOFs were identified.

Recent approaches for the synthesis of heterocycles from amidines via a metal catalyzed C-H functionalization reaction.

Transition metal catalyzed C-H bond activation has become one of the most important tools for constructing new chemical bonds. Introducing directing groups to the substrates is the key to a successful reaction, these directing groups can also be further transformed in the reaction. Amidines with their unique structure and reactivity are ideal substrates for transition metal-catalyzed C-H transformations. This review describes the major advances and mechanistic investigations of the C-H activation/annulation tandem reactions of amidines until early 2024, focusing on metal-catalyzed C-H activation of amidines with unsaturated compounds, such as alkynes, ketone, vinylene carbonate, cyclopropanols and their derivatives. Meanwhile this manuscript also explores the reaction of amidines with different carbene precursors, for example diazo compounds, azide, triazoles, pyriodotriazoles, and sulfoxonium ylides as well as their own C-H bond activation/cyclization reactions. A bright outlook is provided at the end of the manuscript.

Three mutations repurpose a plant karrikin receptor to a strigolactone receptor.

Uncovering the basis of small-molecule hormone receptors' evolution is paramount to a complete understanding of how protein structure drives function. In plants, hormone receptors for strigolactones are well suited to evolutionary inquiries because closely related homologs have different ligand preferences. More importantly, because of facile plant transgenic systems, receptors can be swapped and quickly assessed functionally in vivo. Here, we show that only three mutations are required to turn the nonstrigolactone receptor, KAI2, into a receptor that recognizes the plant hormone strigolactone. This modified receptor still retains its native function to perceive KAI2 ligands. Our directed evolution studies indicate that only a few keystone mutations are required to increase receptor promiscuity of KAI2, which may have implications for strigolactone receptor evolution in parasitic plants.

Mortality salience enhances neural activities related to guilt and shame when recalling the past.

Mortality salience (MS) influences cognition and behavior. However, its effect on emotion (especially moral emotions) and the underlying neural correlates are unclear. We investigated how MS priming modulated guilt and shame in a later recall task using functional magnetic resonance imaging. The behavioral results indicated that MS increased self-reported guilt but not shame. The neural results showed that MS strengthened neural activities related to the psychological processes of guilt and shame. Specifically, for both guilt and shame, MS increased activation in a region associated with self-referential processing (ventral medial prefrontal cortex). For guilt but not shame, MS increased the activation of regions associated with cognitive control (orbitofrontal cortex) and emotion processing (amygdala). For shame but not guilt, MS decreased brain functional connectivity related to self-referential processing. A direct comparison showed that MS more strongly decreased a functional connectivity related to self-referential processing in the shame than in the guilt condition. Additionally, the activation of insula during MS priming was partly predictive of neural activities related to guilt and shame in the subsequent recall task. Our study sheds light on the psychological and neural mechanisms of MS effects on moral emotions and provides theoretical insights for enriching terror management theory.

Profile Autonomous Underwater Vehicle System for Offshore Surveys.

Offshore marine engineering, offshore aquaculture, and offshore environmental protection require periodic offshore surveys. At present, the main means of offshore marine surveys are mooring buoys and marine survey ships. Anchored buoys are fixed in place for a long time, which affects the navigation of ships. Therefore, mooring buoys cannot be deployed over a large area with high density. The cost of marine survey ships is high, especially when multipoint synchronous marine surveys are needed, and marine survey ships cannot perform offshore surveys under bad sea conditions. A profile autonomous underwater vehicle system is developed to meet the requirements of multipoint short-term synchronous offshore surveys. It is a small, reusable, low-cost equipment designed to move up and down at a mooring position while measuring temperature, salinity, depth, and other quantities along a vertical water section. Profile autonomous underwater vehicles can be commanded remotely and report their measurements in near real-time via wireless telemetry. The time it takes for a profile AUV to move up and down can indicate the current velocity. Tests were carried out on a wharf and in offshore areas, and the results were satisfactory.

Robust Sparse Bayesian Two-Dimensional Direction-of-Arrival Estimation with Gain-Phase Errors.

To reduce the influence of gain-phase errors and improve the performance of direction-of-arrival (DOA) estimation, a robust sparse Bayesian two-dimensional (2D) DOA estimation method with gain-phase errors is proposed for L-shaped sensor arrays. The proposed method introduces an auxiliary angle to transform the 2D DOA estimation problem into two 1D angle estimation problems. A sparse representation model with gain-phase errors is constructed using the diagonal element vector of the cross-correlation covariance matrix of two submatrices of the L-shaped sensor array. The expectation maximization algorithm derives unknown parameter expression, which is used for iterative operations to obtain off-grid and signal precision. Using these parameters, a new spatial spectral function is constructed to estimate the auxiliary angle. The obtained auxiliary angle is substituted into a sparse representation model with gain and phase errors, and then the sparse Bayesian learning method is used to estimate the elevation angle of the incident signal. Finally, according to the relationship of the three angles, the azimuth angle can be estimated. The simulation results show that the proposed method can effectively realize the automatic matching of the azimuth and elevation angles of the incident signal, and improves the accuracy of DOA estimation and angular resolution.

Increased ten-eleven translocation methylcytosine dioxygenase one in dorsal root ganglion contributes to inflammatory pain in CFA rats.

DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in neurons in mammals. However, effects of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) expression and hydroxymethylation status on neuron injury remain unclear. This study was designed to explore the effects of TET1 and TET2 expression in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA). Mechanical paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) were detected to assess pain behavior. The expression of TET1 and TET2 were measured in the dorsal root ganglion (DRG) with western blotting analysis. Immunofluorescence staining is employed to detect the expression and co-location of TRPV1 with TET1. Intrathecal administration of Bobcat339 was used to inhibit TET1 function in dorsal root ganglion. The paw withdrawal threshold and thermal withdrawal latency of rats were significantly reduced after CFA Injection. Western blot results showed that the expression of TET1 was significantly increased at 3 days after CFA injection, but TET2 had no statistical difference. Immunofluorescence results showed that TET1 was co-localized with TRPV1. Intrathecal administration of Bobcat339 improved mechanical and thermal pain threshold in CFA rats. Our findings highlight the role of TET1 in chronic inflammatory pain model. The expression of TET1 was increased in CFA rats, and suppression of TET1 will ameliorate inflammatory pain.

Population pharmacokinetics analysis of guselkumab in healthy subjects and patients with psoriatic arthritis, plaque psoriasis and palmoplantar pustulosis.

AIMS: Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin 23, is approved for the treatment of plaque psoriasis (PsO) and psoriatic arthritis (PsA), palmoplantar pustulosis (PPP), generalized pustular psoriasis, and erythrodermic psoriasis in various countries. The purpose of this analysis was to develop a comprehensive population pharmacokinetic (PK) model for guselkumab to determine whether PK differs across different disease populations and healthy subjects. METHODS: A nonlinear mixed-effects modelling approach was used to analyse 23 097 serum PK samples obtained from 2623 healthy subjects and patients with PsO, PsA and PPP across 9 phase 1-3 clinical trials. RESULTS: Guselkumab concentrations were adequately described by a 2-compartment linear PK model with first-order absorption and elimination. Clearance (CL), central and peripheral volume of distribution, intercompartmental flow, absorption rate constant and absolute bioavailability estimates were 0.255 L/d, 3.60 L, 1.78 L, 0.369 L/d, 0.313 d-1 and 49.2%, respectively, for a subject weighing 70 kg. Terminal half-life was estimated to be approximately 14.6 days. Body weight was the primary factor affecting CL and central volume of distribution. CL of guselkumab was similar among patients with PsA, PsO and PPP, but CL in disease populations was 11-17% lower than that in healthy subjects after other covariate effects such as body weight were considered. CONCLUSION: The population pharmacokinetic analysis indicated that, after other covariate effects were taken into account, patients with PsO, PsA and PPP had similar PK characteristics, with CL in these disease populations being slightly lower than in healthy individuals.

Synthesis of Water-Soluble Sulfonated Chitin Derivatives for Potential Antioxidant and Antifungal Activity.

Chitin is a natural renewable and useful biopolymer limited by its insolubility; chemical derivatization can enhance the solubility and bioactivity of chitin. The purpose of this study was to synthesize novel water-soluble chitin derivatives, sulfo-chitin (SCT) and sulfopropyl-chitin (SPCT), as antioxidant and antifungal agents. The target derivatives were characterized by means of elemental analysis, FTIR, 13C NMR, TGA and XRD. Furthermore, the antioxidant activity of the chitin derivatives was estimated by free radical scavenging ability (against DPPH-radical, hydroxyl-radical and superoxide-radical) and ferric reducing power. In addition, inhibitory effects against four fungi were also tested. The findings show that antioxidant abilities and antifungal properties were in order of SPCT > SCT > CT. On the basis of the results obtained, we confirmed that the introduction of sulfonated groups on the CT backbone would help improve the antioxidant and antifungal activity of CT. Moreover, its efficacy as an antioxidant and antifungal agent increased as the chain length of the substituents increased. This derivatization strategy might provide a feasible way to broaden the utilization of chitin. It is of great significance to minimize waste and realize the high-value utilization of aquatic product wastes.

Transcultural adaptation and psychometric properties of Chinese version of Death Depression Scale-Revised among nursing students.

The study aimed to determine the psychometric properties of the Chinese version of the Death Depression Scale in a sample of 391 nursing students. The Cronbach's alpha coefficient was 0.91, ranging from 0.65 to 0.91 for each subscale. Test-retest reliability was satisfactory (r = 0.821). Overall content validity index was 0.83. An exploratory factor analysis yielded 5 factors: anergia and anhedonia, death sadness, other death, death emptiness, and death vacuum. The model had an acceptable fit, with all factors loading greater than 0.5. Results provide preliminary support for the reliability and validity of the measure in nursing student populations.

From gratitude to injustice: Neurocomputational mechanisms of gratitude-induced injustice.

Gratitude shapes individuals' behaviours and impacts the harmony of society. Many previous studies focused on its association with prosocial behaviours. A possibility that gratitude can lead to moral violation has been overlooked until recently. Nevertheless, the neurocognitive mechanisms of gratitude-induced moral violation are still unclear. On the other hand, though neural correlates of the gratitude's formation have been examined, the neural underpinnings of gratitude-induced behaviour remain unknown. For addressing these two overlapped research gaps, we developed novel tasks to investigate how participants who had received voluntary (Gratitude group) or involuntary help (Control group) punished their benefactors' unfairness with functional magnetic resonance imaging (fMRI). The Gratitude group punished their benefactors less than the Control group. The self-report and computational modelling results demonstrated a crucial role of the boosted protection tendency on behalf of benefactors in the gratitude-induced injustice. The fMRI results showed that activities in the regions associated with mentalizing (temporoparietal junction) and reward processing (ventral medial prefrontal cortex) differed between the groups and were related to the gratitude-induced injustice. They suggest that grateful individuals concern for benefactors' benefits, value chances to interact with benefactors, and refrain from action that perturbs relationship-building (i.e., exert less punishment on benefactors' unfairness), which reveal a dark side of gratitude and enrich the gratitude theory (i.e., the find-bind-remind theory). Our findings provide psychological, computational, and neural accounts of the gratitude-induced behaviour and further the understanding of the nature of gratitude.

Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To assess efficacy, pharmacokinetics (PK) and safety of intravenous (i.v.) golimumab in patients with polyarticular-course JIA (pc-JIA). METHODS: Children aged 2 to <18 years with active pc-JIA despite MTX therapy for ≥2 months received 80 mg/m2 golimumab at weeks 0, 4, then every 8 weeks through week 52 plus MTX weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at weeks 28 and 52, respectively. JIA ACR response and safety were also assessed. RESULTS: In total, 127 children were treated with i.v. golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70% and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg ⋅ day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to i.v. golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including one death due to septic shock. CONCLUSION: Body surface area-based dosing of i.v. golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.

Copper-catalyzed three-component formal [3 + 1 + 2] annulations for the synthesis of 2-aminopyrimidines from O-acyl ketoximes.

A copper-based catalytic system has been developed to enable formal [3 + 1 + 2] annulations of ketoxime acetates, aldehydes, and cyanamides. This protocol offers a new strategy for the synthesis of highly substituted 2-aminopyrimidine compounds, and more importantly, pyrimidines have now been included in the N-heterocycle family constructed using O-acyl ketoximes as N-C-C synthons.

The effect of catalytic copper pretreatments on CVD graphene growth at different stages.

The controllable synthesis of high-quality and large-area graphene by chemical vapor deposition (CVD) remains a challenge nowadays. The massive grain boundaries in graphene grown on polycrystalline Cu by CVD significantly reduce its carrier mobility, limiting its application in high-performance electronic devices. Here, we confirm that the synergetic pretreatment of Cu with electropolishing and surface oxidation is a more efficient way to further suppress the graphene nucleation density (GND) and to accelerate the growth rate of the graphene domain by CVD. With increasing the growth time, we found that the increasing amount of GND and growth rate of the graphene domain were both decreasing during the whole CVD process when the Cu surface was not oxidized. By contrast, they kept growing over time when the Cu surface was pre-oxidized, which suggested that the change trends of the effects on the GND and growth rate between the Cu surface morphology and oxygen were opposite in the CVD process. In addition, not only the domain shape, but the number of graphene domain layers were impacted as well, and a large number of irregular ellipse graphene wafers with dendritic multilayer emerged when the Cu surface was oxidized.

Machine learning for predicting preoperative red blood cell demand.

BACKGROUND: The paucity of accurate quantitative standards for determining the quantity of red blood cells (RBCs) needed for perioperative patients and the predominant application of the "preoperative hemoglobin + surgery type" empirical decision-making model have led to widespread RBC application problems. OBJECTIVE: The mathematical model of preoperative variables constructed by machine learning (ML) methods can help doctors decide preoperative RBC applications. METHODS: We retrospectively analysed 130 996 records of patients who received surgery in our hospital from January 2011 to June 2017. Through the analysis of multiple preoperative parameters that may affect the RBC transfusion volume, we used ML algorithms to build up the artificial intelligence (AI) model to predict the accurate RBC demand quantity and compared each result with those predicted by clinicians. RESULTS: Among the seven ML algorithms, the light gradient boosting machine (Lightgbm) algorithm was the best. The AI model predicted whether the patients needed RBC transfusion, and the area under curve (AUC) was 0.908 (95% CI 0.907-0.913). The AI model was more accurate than doctors in predicting RBC of 0, 2, and 4 units (85% data), with RMSEs of 1.61 vs. 2.15, 1.06 vs. 1.21, and 1.46 vs. 1.68, respectively. However, the AI model was not better than doctors in 1, 3, 5-6, 7-8, and 9-10 units (15% data), with RMSEs of 0.92 vs. 0.89, 0.92 vs. 0.89, 2.73 vs. 1.94, 4.53 vs. 3.92, and 6.26 vs. 5.08, respectively. CONCLUSION: Through the comparison of seven ML methods, the Lightgbm algorithm-based model is more accurate than clinician experience-based in predicting preoperative RBC transfusion, which reduces the risk of untimely blood supply caused by insufficient preoperative blood preparation, and reduces the unnecessary cost of blood compatibility testing caused by excessive preoperative blood preparation.

Radical 1,4-Aryl Migration Enabled Remote Cross-Electrophile Coupling of α-Amino-ß-Bromo Acid Esters with Aryl Bromides.

We report an unprecedented, efficient nickel-catalysed radical relay for the remote cross-electrophile coupling of ß-bromo-α-benzylamino acid esters with aryl bromides via 1,4-aryl migration/arylation cascades. ß-Bromo-α-benzylamino acid esters are considered as unique molecular scaffolds allowing for aryl migration reactions, which are conceptually novel variants for the radical Truce-Smiles rearrangement. This reaction enables the formation of two new C(sp3 )-C(sp2 ) bonds using a bench-stable Ni/bipyridine/Zn system featuring a broad substrate scope and excellent diastereoselectivity, which provides an effective platform for the remote aryl group migration and arylation of amino acid esters via redox-neutral C(sp3 )-C(sp2 ) bond cleavage. Mechanistically, this cascade reaction is accomplished by combining two powerful catalytic cycles consisting of a cross-electrophile coupling and radical 1,4-aryl migration through the generation of C(sp3 )-centred radical intermediates from the homolysis of C(sp3 )-Br bonds and the switching of the transient alkyl radical into a robust α-aminoalkyl radical.

Ustekinumab Pharmacokinetics and Exposure Response in a Phase 3 Randomized Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: The efficacy of antibody-based therapeutics depends on their pharmacokinetics. The pharmacokinetic and exposure response profiles of ustekinumab, a monoclonal antibody against interleukin 12/interleukin 23, are known in patients with Crohn's disease, yet there are few data from patients with ulcerative colitis. We characterized ustekinumab's pharmacokinetics, exposure response, and optimal serum concentrations in patients with ulcerative colitis. METHODS: We collected data from 2 phase 3 trials (1 induction and 1 maintenance), in which patients with moderate to severe ulcerative colitis received an intravenous induction dose of ustekinumab (130 mg, n = 320; or approximately 6 mg/kg, n = 322). Responders were assigned randomly to groups that received subcutaneous maintenance ustekinumab (90 mg) every 8 weeks (n = 176) or 12 weeks (n = 172), or placebo (n = 175). We evaluated the association between ustekinumab concentration and efficacy, serum based on clinical effects (Mayo score), histologic features, and inflammation (measurement of C-reactive protein, fecal calprotectin, and fecal lactoferrin), as well as safety (infections, serious infections, and serious adverse events), during induction and maintenance therapy. Optimal serum concentrations of ustekinumab were identified using receiver operating characteristic curve analyses. RESULTS: In patients with ulcerative colitis, dose-proportional serum concentrations of ustekinumab, unaffected by prior biologic or concomitant immunomodulator therapy, reached steady state by the second maintenance dose; the median trough concentration for dosing every 8 weeks was approximately 3-fold that of dosing every 12 weeks. Serum concentrations were associated with clinical and histologic features of efficacy and normalization of inflammation markers. The week-8 concentration threshold for induction of response was 3.7 µg/mL. A steady-state trough serum concentration of 1.3 µg/mL or higher was associated with a higher rate of clinical remission compared with patients who had lower serum concentrations. Serum concentrations of ustekinumab were not associated with infections, serious infections, or serious adverse events. CONCLUSIONS: In an analysis of data from 2 phase 3 trials of patients with ulcerative colitis, we found that serum concentrations of ustekinumab were proportional to dose, unaffected by prior biologic or concomitant immunomodulator therapies, associated with clinical and histologic efficacy and markers of inflammation, and were not associated with safety events at doses evaluated. Ustekinumab pharmacokinetics are consistent between patients with Crohn's disease vs ulcerative colitis.