Structural insights into the ubiquitylation strategy of the oligomeric CRL2FEM1B E3 ubiquitin ligase.

Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2FEM1B in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2FEM1B is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2FEM1B. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2FEM1B according to substrates with different scales.

Biogenic elements-informed assessment of the impact of human activities on river ecosystems.

River ecosystems, acting as pivotal conduits linking terrestrial, marine, and atmospheric realms, have faced significant disturbances due to human exploitation of their resources. Recent years have witnessed a heightened intensification of human activities, adversely affecting the equilibrium of water ecosystems. To systematically study the various factors that affect river ecosystems under human activities, we introduce a universally applicable approach that considers the diversity of watersheds, biogenic elements, and human activities. Using this method, this application uncovers the sensitive human activity types, biogenic factors, and species significantly influencing river biodiversity within the study area. Incorporating statistical modelling, sensitivity screening, and advanced correlation analyses within a random forest regression framework, Sensitive biogenic elements and biological types affected by human activities were identified in typical watersheds, and the stability of different aquatic ecosystems was evaluated. Suggestions for watershed management measures were proposed When human activities affect the degree of water resource development and utilization, the forms of sensitive biogenic elements include DIC and Tsi; When human activities affect the discharge of pollutants into rivers, the forms of sensitive biogenic elements include TP, PP, and DEP, and the ratio composition includes TC: TN, TC: TP, TP: TSi, and TN: TP, This study pioneers a novel method for assessing human impacts on river ecosystems and successfully applies this approach to inform management decisions for river segments and tributaries in the middle and upper reaches of the Yangtze River basin. thereby enhancing our understanding of the consequences of human-induced impacts on biodiversity.

Aromatic Terpenes and Their Biosynthesis in Dendrobium, and Conjecture on the Botanical Perfumer Mechanism.

This review presents a systematic analysis of the studies on volatiles in Dendrobium. Among the various components, aromatic terpenes are a crucial component in the development of the aromatic characteristics of Dendrobium and other plants. Recent advancements in detection and sequencing technology have resulted in a considerable rise in research on the biosynthetic processes of aromatic terpenes in Dendrobium and other flowering plants. Nevertheless, the inquiry into the precise means by which plants regulate the proportion of diverse aromatic terpenes in their floral scent, thereby preserving their olfactory traits, requires further investigation. A conjecture on the botanical perfumer mechanism, which condensed the findings of earlier studies, was put forward to address this area of interest. Specific transcription factors likely govern the coordinated expression of multiple key terpene synthase (TPS) genes during the flowering stage of plants, thereby regulating the proportional biosynthesis of diverse aromatic terpenes and sustaining the distinctive aromatic properties of individual plants. This review serves as a significant theoretical reference for further investigations into aromatic volatile compounds in Dendrobium.

Discriminatory Gate-Opening Effect in a Flexible Metal-Organic Framework for Inverse CO2 /C2 H2 Separation.

Considering the significant application of acetylene (C2 H2 ) in the manufacturing and petrochemical industries, the selective capture of impurity carbon dioxide (CO2 ) is a crucial task and an enduring challenge. Here, a flexible metal-organic framework (Zn-DPNA) accompanied by a conformation change of the Me2 NH2 + ions in the framework is reported. The solvate-free framework provides a stepped adsorption isotherm and large hysteresis for C2 H2 , but type-I adsorption for CO2 . Owing to their uptakes difference before gate-opening pressure, Zn-DPNA demonstrated favorable inverse CO2 /C2 H2 separation. According to molecular simulation, the higher adsorption enthalpy of CO2 (43.1 kJ mol-1 ) is due to strong electrostatic interactions with Me2 NH2 + ions, which lock the hydrogen-bond network and narrow pores. Furthermore, the density contours and electrostatic potential verifies the middle of the cage in the large pore favors C2 H2 and repels CO2 , leading to the expansion of the narrow pore and further diffusion of C2 H2 . These results provide a new strategy that optimizes the desired dynamic behavior for one-step purification of C2 H2 .

Engineering of Stable Anionic/Neutral MOFs with Zinc-Adeninate Building Units for Efficient C2H2/CO2 Separation.

Using adenine and metal ions to form secondary building units (SBUs), further connected by a highly symmetrical multicarboxylic linker to construct an amino-modified porous framework with high porosity, is an effective strategy. By regulating the deprotonation and hydrolysis capacity of the synthesized solvent, it is possible to obtain different charged frameworks. In this work, two stable anionic/neutral MOFs, (Et2NH2)[Zn3(TCPE)(adenine)2CH3COO]·DEF·3H2O (1) and [Zn3.5(adenine)(TCPE)1.5(DMA)(H2O)0.5]·2DMA·2H2O (2), have been synthesized based on zinc-adeninate building units and symmetric tetrakis(4-carboxyphenyl)ethylene (H4TCPE) in N,N-diethylformamide (DEF) and N,N-dimethylacetamide (DMA) reaction systems, respectively. 1 is an anionic framework based on 1D rod zinc-adeninate SBU, containing 1D rectangular (14.3 × 6.3 Å2) and square (14.3 × 14.3 Å2) channels. While 2 is a neutral framework built from isolated zinc-adeninate SBU, it contains hexagonal cages with a dimension of 5.5 Å in the structure. Both of them have high porosity (61.6% for 1 and 46.3% for 2) and high stability in a wide range of pH. 1 and 2 show high C2H2 adsorption capacity at 298 K (48.1 and 70.1 cm3 g-1, respectively) and selective capacity for C2H2/CO2 mixtures, which was confirmed by the breakthrough experiments. Furthermore, the interaction between the frameworks and gas molecules has also been explained by theoretical calculation. This work provides a good example of the design and regulation of porous structures for adsorption and separation functions.

Alcohol use severity among recent Latino immigrants: Associations of acculturation, family history of alcohol use and alcohol outcome expectancies.

Having a family history of alcohol (FH+) use is a well-documented risk factor for alcohol use and alcohol related problems. However, there are limited studies examining the impact of FH + on current alcohol use among Latino immigrants. This study aimed to determine the influence of having a FH + on current alcohol use among Latino immigrants and the influence of alcohol outcome expectancies (AOEs) and acculturation on this relationship. This is a longitudinal secondary data analysis of data from the Recent Latino Immigrant Study (RLIS), the first community-based cohort study to examine pre- to post-immigration alcohol use trajectories of young adult Latino immigrants. Linear mixed models were performed to assess the association between various pre- and post-immigration factors and alcohol use among Latino immigrants. There were 518 young adult Latino immigrants with 18.7% reporting a FH + with those with a FH + having higher mean AUDIT score compared to those without (4.74 vs. 3.81; p = 0.028). Positive AOEs were associated with increase AUDIT scores. FH + individuals with greater positive AOEs experienced higher AUDIT scores compared to FH- individuals. Family cohesion was protective against alcohol use while endorsement of Americansism was associated with increased alcohol use. Theses results provide the framework for more in-depth exploration regarding the influences of FH+, AOEs, and acculturation have on the alcohol use among Latino immigrants. Future longitudinal research studies should account for whether traditional cultural values mediate or moderate the relationship between a FH+, AOE, and alcohol use of Latino immigrants.

Hexagonal Cages and Lewis Acid-Base Sites in a Metal-Organic Framework for Synergistic CO2 Capture and Conversion under Mild Conditions.

The cycloaddition reaction of carbon dioxide (CO2) is a highly economic solution to becoming carbon-neutral. Herein, we have designed and synthesized a robust zinc(II)-organic framework (Zn-Ade-TCPE) by a function-directed strategy. Zn-Ade-TCPE possesses uncommon hexagonal cages with Lewis acid-base bifunctional sites and displays a high adsorption capacity for CO2. At room temperature and atmospheric pressure, Zn-Ade-TCPE exhibits outstanding activity, selectivity, and recyclability in the cycloaddition reaction of epoxides with CO2 because of the synergistic effect of multiple active sites and confined cavities.

Pre- and post-immigration factors associated with cigarette use among young adult recent Latinx immigrants during their initial year in the U.S.

Background: Evidence indicates escalating rates of cigarette use among foreign-born Latinx as their time in the U.S increases. As such, it's important to understand shifts in pre- to post-immigration smoking patterns early in the immigration process and its associated factors.Objectives: To examine 1) cigarette use among recent Latinx immigrants (RLIs) during their initial year in the U.S.; 2) whether cigarette use after immigration is influenced by smoking patterns in immigrant's country of origin; and 3) associations between pre/post immigration sociocultural factors and changes in cigarette use after immigration.Methods: Baseline data were utilized from an on-going longitudinal study of 540 young adult (50% females) RLIs. Inclusion criteria was being between ages 18 and 34, residing in Miami-Dade County, Florida, and having immigrated from a Latin American country within the past yearResults: Approximately 31% of participants reported being smokers in their country of origin while 26% were current smokers (while residing in the U.S). Post-immigration cigarette use was substantially influenced by country of origin cigarette use (V = .68); 84% of pre-immigration smokers reported no change in smoking frequency, while 11% lowered and 6% increased their cigarette use post-immigration. Reduction in smoking after immigration was more likely among participants with higher pre-immigration social support (aOR = 1.87) and less likely among those residing in high-crime neighborhoods (aOR = .84).Conclusion: Interventions aimed to discourage cigarette use should begin early in the immigration process and account for RLIs' pre-immigration smoking patterns. Interpersonal supports and neighborhood contextual factors should be considered when developing smoking cessation programs with this population.

Pulsed terahertz spectroscopy combined with hybrid machine learning approaches for structural health monitoring of multilayer thermal barrier coatings.

Structural health monitoring of multilayer thermal barrier coatings (TBCs) is very vital to ensure the structural integrity and service performance of the hot-section components of the aero-engine. In this paper, we theoretically and numerically demonstrated that the terahertz time domain spectrum and the terahertz reflectance spectrum could be adopted to estimate the structure parameters, based on the finite difference time domain (FDTD) algorithm, 64 samples which were imported with three kinds of 64 sets structure parameters had been calculated to obtain the time domain and terahertz reflectance signals. To mimic the actual test signals, the original FDTD simulation signals were processed by adding the Gaussian white noise and wavelet noise reduction. To reduce the data dimension and improve the calculation efficiency during modeling, the principal component analysis (PCA) algorithm was adopted to reduce the dimensions of time-domain data and reflectance data. Finally, these data after multiple signal processing and PCA feature extraction were used to train the extreme learning machine (ELM), combining the genetic algorithm (GA) could optimize the PCA-ELM model and further improve the prediction performance of the hybrid model. Our proposed novel and efficient terahertz nondestructive technology combined with the hybrid machine learning approaches provides great potential applications on the multilayer TBCs structural integrity evaluation.

Evaluating the Humpty Dumpty Fall Scale: An International, Multisite Study.

BACKGROUND: The Humpty Dumpty Falls Prevention Program was developed to address an unmet need to identify pediatric patients at risk of a fall event. PURPOSE: The aim of this study was to evaluate the performance of the Humpty Dumpty Fall Scale-Inpatient (HDFS) across a diverse, international pediatric population. In addition, the characteristics of patients who experienced a fall were analyzed. METHODS: A retrospective, cross-sectional design was used to assess fall risk across 16 hospitals and 2238 pediatric patients. Multiple and simple logistic regressions were performed to evaluate association of individual scale items and total score with falls during hospitalization. Reliability, sensitivity, and specificity of the HDFS were also assessed. RESULTS: Several of the HDFS items were significantly associated with the risk of falls in the pediatric population, but specificity of the tool is a concern to consider for future tool enhancement. CONCLUSIONS: Characteristics for further refinement of the HDFS were identified.

The Relationship Between Housing Status and Substance Use and Sexual Risk Behaviors Among People Currently Seeking or Receiving Services in Substance Use Disorder Treatment Programs.

Although HIV risk behaviors such as substance use and condomless sex are prevalent among people currently seeking or receiving services at substance use disorder (SUD) treatment programs, associations with housing status in this population have not been well studied. We examined the associations between housing status, substance use and HIV-related sexual risk behaviors among 1281 participants from 12 US community-based SUD programs. In addition, substance use was examined as a potential mediator of the relationship between housing status and sexual risk behaviors. We conducted Chi-square, univariate and multivariate logistic regression models on data from the National Drug Abuse Treatment Clinical Trials Network HIV Rapid Testing and Counseling study. Path analysis was used to test the mediation and indirect effects. Unstable housing was significantly associated with having multiple concurrent condomless sex partners, condomless sex with non-primary partners, and partners of unknown HIV serostatus. Homelessness was significantly associated with condomless vaginal sex and condomless sex with any substance use. The path between unstable housing and sexual risk behaviors was mediated by problematic drug use, particularly by cocaine, opioids, and marijuana use. Because housing status impacts HIV risk behaviors for individuals in SUD treatment programs, both housing status and substance use behaviors should be assessed upon program entry in order to identify and mitigate risk behaviors.

In-situ evaluation of porosity in thermal barrier coatings based on the broadening of terahertz time-domain pulses: simulation and experimental investigations.

Porosity is one of the most important indicators for the characterization of the comprehensive performance of thermal barrier coatings (TBCs). Herein, we explored a fast, nondestructive porosity evaluation method based on the terahertz time-domain broadening effect. Different preparation process parameters were used to deposit the ceramic coatings, and the porosity ranged from 9.09% to 21.68%. Monte Carlo simulations were conducted to reveal the transitive relation between porosity and the terahertz time-domain broadening at different extinction coefficients and transmission distances. A transmission mode with an incidence angle of 0° was used to estimate the terahertz dielectric properties of ceramic coatings and the relative broadening ratio of terahertz pulses at different porosities. As a result, the Monte Carlo simulations showed that the time-domain broadening effect was enhanced when the extinction coefficient and transmission distances increased. As the porosity increased, the refractive index decreased and the extinction coefficient increased. The latter was more sensitive to minor porosity changes as demonstrated by linear fitting comparisons. Meanwhile, the relative broadening ratio increased when the porosity increased, and reserved the sensitivity of the extinction coefficient to porosity changes. The effect was more obvious on the relative broadening ratio which experienced multiple transmissions and reflections. Moreover, the relative broadening ratio could be obtained faster and in an easier manner compared to the dielectric parameters in both the transmission and reflection modes, based on single-step tests with the use of actual terahertz wave inspection. Finally, this study proposed a novel, convenient, online, nondestructive, and noncontact porosity evaluation method that could be potentially utilized to evaluate the integrity of TBCs in gas turbine blades.

Two Stable Terbium-Organic Frameworks Based on Predesigned Functionalized Ligands: Selective Sensing of Fe3+ Ions and C2H2/CH4 Separation.

To construct desired metal-organic framework (MOF) sensors, the predesigned functionalized ligands 2,5-bis(2',5'-dicarboxylphenyl)pyridine (L-N) and 2,5-bis(2',5'-dicarboxylphenyl)difluorobenzene (L-F) with pyridine- and fluorine-decorated tetracarboxylic acids were used, and two stable terbium-organic frameworks, H3O[(Tb(L-N)(H2O)2]·2H2O (Tb-N) and [Tb3(L-F)2(HCOO)(H2O)4]·6H2O (Tb-F), have been synthesized. The structures of Tb-N and Tb-F contain 1D open channels, which are functionalized by pyridine N or F atoms, respectively. Both of them show intense fluorescence in water and exhibit excellent selectivity and sensitivity to Fe3+ ions. The effects of different functional group sites on the stability and fluorescence sensing performance of MOFs have also been studied. In addition, a gas adsorption study demonstrates that Tb-N is capable of adsorbing C2H2 over CH4 selectively.

One-step synthesis and deposition of ZnFe2O4 related composite films via SPPS route for photodegradation application.

Binary spinel-type metal oxides (AB2O4) related materials, including ferrites (AFe2O4), are attractive photocatalysts thanks to their excellent visible light response for the photodegradation of organic pollutants. Currently, these materials are synthesized via conventional chemical routes suffering from long preparation duration and multistep. Moreover, the photocatalysts are obtained as nano-powders from conventional chemical routes would introduce another drawback for their recycling and reuse. From an industrial perspective, it is desirable to develop an efficient and facile synthesis process to produce photocatalysts in a non-dispersible form. Herein, we demonstrate that the solution precursor plasma spray (SPPS) process is a single-step method for depositing photocatalytically active zinc ferrite-based films within several minutes. The influence of the precursor ratio on the microstructures and phase compositions of the ZnFe2O4 films was investigated by XRD and Raman analyses. In addition, two optimized ZnFe2O4 films were prepared by increasing the ZnO loading and tailoring injection pattern of the precursor solution. The surface morphologies and optical bandgap were also determined by SEM and UV-visible spectroscopy. The photocatalytic activities of the ZnFe2O4 films were evaluated through the degradation of the Orange II dye and of tetracycline hydrochloride under UV or visible light irradiation. The results show that compositional ratios and composition distribution of the ZnFe2O4 films prepared via SPPS played a key role on the photocatalytic activity. The SPPS route was demonstrated to be a promising method for the synthesis and the deposition of metal oxide (i.e. perovskite type and spinel type) films within a single-step for functional applications.

Gender Differences in HIV Sexual Risk Behaviors Among Clients of Substance Use Disorder Treatment Programs in the U.S.

This study examined differences in sexual risk behaviors by gender and over time among 1281 patients (777 males and 504 females) from 12 community-based substance use disorder treatment programs throughout the United States participating in CTN-0032, a randomized control trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Zero-inflated negative binomial and negative binomial models were used in the statistical analysis. Results indicated significant reductions in most types of sexual risk behaviors among substance users regardless of the intervention arms. There were also significant gender differences in sexual risk behaviors. Men (compared with women) reported more condomless sex acts with their non-primary partners (IRR = 1.80, 95 % CI 1.21-2.69) and condomless anal sex acts (IRR = 1.74, 95 % CI 1.11-2.72), but fewer condomless sex partners (IRR = 0.87, 95 % CI 0.77-0.99), condomless vaginal sex acts (IRR = 0.83, 95 % CI 0.69-1.00), and condomless sex acts within 2 h of using drugs or alcohol (IRR = 0.70, 95 % CI 0.53-0.90). Gender-specific intervention approaches are called for in substance use disorder treatment.

Age Differences in the Trends of Smoking Among California Adults: Results from the California Health Interview Survey 2001-2012.

The aim is to study the trends of cigarette smoking from 2001 to 2012 using a California representative sample in the US. Data was taken from the California Health Interview Survey (CHIS) from 2001 to 2012, which is a population-based, biennial, random digit-dial telephone survey of the non-institutionalized population. The CHIS is the largest telephone survey in California and the largest state health survey in the US. 282,931 adults (n = 184,454 with age 18-60 and n = 98,477 with age >60) were included in the analysis. Data were weighted to be representative and adjusted for potential covariance and non-response biases. During 2001-2012, the prevalence of current smoking decreased from 18.86 to 15.4 % among adults age 18-60 (ß = -0.8, p = 0.0041). As for adults age >60, the prevalence of current smoking trend decreased with variations, started from 9.66 % in 2001, slightly increased to 9.74 % in 2003, but then gradually decreased, falling to 8.18 % in 2012. In 2012, there was a 14 % reduction of daily smoking adults age 18-60 (OR 0.84, 95 % CI 0.76-0.93, p = 0.0006) compared to 2001, while no significant reduction of daily smoking was observed for those age >60. The reductions of smoking prevalence for adults younger than 60 are encouraging. However, there is a concern for smoking cessation rates among those older than 60 years of age, particularly for African Americans.

Impact of transforming karst mountainous forests into urban parks on plant diversity patterns.

The conversion of urban montane forest resources into urban parks requires careful assessment to understand its impacts on plant diversity over time. This study aims to enhance urban biodiversity conservation strategies by analyzing how habitat type and park age affect woody plant diversity. We surveyed woody plant species in 60 sample plots across two different habitats (remnant forest vs. artificial green space) within three mountain parks in Guiyang, China, established at different times. The alpha diversity of saplings/seedlings was significantly higher in remnant forests than in artificial green spaces. Artificial green spaces exhibited more homogenous woody plant composition compared with remnant forests. Newer parks showed greater variation in plant composition between the two habitats than older parks. Indicative species in remnant forests were predominantly native, whereas those in artificial green spaces were mainly ornamental species. The transformation of karst mountainous forests into urban parks leads to the homogenization of woody plant composition and impedes the regeneration of saplings/seedlings. Therefore, it is crucial to manage these conversions carefully and strive to preserve as many native species as possible to support urban plant diversity conservation.

Drug delivery system based on metal-organic framework improved 5-Fluorouracil against spring viremia of carp virus.

Spring viremia of carp virus (SVCV), as a high pathogenicity pathogen, has seriously restricts the healthy and sustainable development of cyprinid farming industry. In this study, we selected 5-Fluorouracil (5-Fu) as the drug model based on zeolitic imidazolate framework-8 (ZIF-8) to construct a drug delivery system (5-Fu@ZIF-8), and the anti-SVCV activity was detected in vitro and in vivo. The results showed 5-Fu@ZIF-8 was uniform cubic particle with truncated angle and smooth surface, and the particle size was 90 nm. The anti-SVCV activity in vitro results showed that the highest inhibition rate of 5-Fu was 77.93% at 40 mg/L and the inhibitory concentration at half-maximal activity (IC50) was 20.86 mg/L. For 5-Fu@ZIF-8, the highest inhibition rate was 91.36% at 16 mg/L, and the IC50 value was 5.85 mg/L. In addition, the cell viability was increased by 18.1% after 5-Fu treatment. Similarly, after 5-Fu@ZIF-8 treatment, the cell viability increased by 27.3%. Correspondingly, in vivo experimental results showed the viral loads reduced by 18.1% on the days 7 and the survival rate increased to 19.4% at 80 mg/L after 5-Fu treatment. For 5-Fu@ZIF-8, the viral loads reduced by 41.2% and the survival rate increased to 54.8%. Mechanistically, 5-Fu inhibits viral replication by regulating p53 expression and promoting early apoptosis in infected cells. All results indicated that 5-Fu@ZIF-8 improved the anti-SVCV activity; it may be a potential strategy to construct a drug-loaded system with ZIF-8 as a carrier for the prevention and treatment of aquatic diseases.

A conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3KLHL22.

The CUL3-RING E3 ubiquitin ligases (CRL3s) play an essential role in response to extracellular nutrition and stress stimuli. The ubiquitin ligase function of CRL3s is activated through dimerization. However, how and why such a dimeric assembly is required for its ligase activity remains elusive. Here, we report the cryo-EM structure of the dimeric CRL3KLHL22 complex and reveal a conserved N-terminal motif in CUL3 that contributes to the dimerization assembly and the E3 ligase activity of CRL3KLHL22. We show that deletion of the CUL3 N-terminal motif impairs dimeric assembly and the E3 ligase activity of both CRL3KLHL22 and several other CRL3s. In addition, we found that the dynamics of dimeric assembly of CRL3KLHL22 generates a variable ubiquitination zone, potentially facilitating substrate recognition and ubiquitination. These findings demonstrate that a CUL3 N-terminal motif participates in the assembly process and provide insights into the assembly and activation of CRL3s.

The immunologic role of IL-23 in psoriatic arthritis: a potential therapeutic target.

INTRODUCTION: Psoriatic arthritis (PsA) is a debilitating chronic condition characterized by inflammation of the joints, bones, enthesis, and skin. The pivotal role of interleukin-23 (IL-23) in the pathogenesis of PsA has become increasingly evident. This proinflammatory cytokine is markedly elevated in patients with PsA, suggesting its potential as a therapeutic target. Consequently, IL-23 inhibitors have emerged as promising first-line biologic treatments for PsA. AREAS COVERED: This review delves into the immunopathogenic mechanisms of IL-23 at the cellular and molecular levels in PsA. Furthermore, it provides the recent efficacy and safety profiles of IL-23 inhibitors. We conducted a literature search in PubMed for the following terms: 'IL-23 and psoriatic arthritis,' 'Ustekinumab,' 'Guselkumab,' 'Risankizumab,' and 'Tildrakizumab.' In addition, we retrieved clinical trials involving IL-23 inhibitors registered in ClinicalTrials.gov, EudraCT, and ICTRP. EXPERT OPINION: Despite the promising outcomes observed with IL-23 inhibitors, several challenges persist. The long-term effects of these agents require further investigation through prospective studies, and their limited accessibility worldwide necessitates urgent attention. Additionally, ongoing research is warranted to explore other potential drug targets within the IL-23/IL-23 R axis. The development of reliable biomarkers could greatly enhance early detection, tailored management strategies, and personalized treatment approaches for patients with PsA.