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Three-dimensional printing technology, also called additive manufacturing technology, is used to prepare personalized 3D-printed drugs through computer-aided model design. In recent years, the use of 3D printing technology in the pharmaceutical field has become increasingly sophisticated. In addition to the successful commercialization of Spritam® in 2015, there has been a succession of Triastek’s 3D-printed drug applications that have received investigational new drug (IND) approval from the Food and Drug Administration (FDA). Compared with traditional drug preparation processes, 3D printing technology has significant advantages in personalized drug manufacturing, allowing easy manufacturing of preparations with complex structures or drug release behaviors and rapid manufacturing of small batches of drugs. This review summaries the mechanisms of the most commonly used 3D printing technologies, describes their characteristics, advantages, disadvantages, and applications in the pharmaceutical industry, analyzes the progress of global commercialization of 3D printed drugs and their problems and challenges, reflects the development trends of the 3D printed drug industry, and guides researchers engaged in 3D printed drugs.

Effective and reliable load forecasting is an important basis for power system planning and operation decisions. Its forecasting accuracy directly affects the safety and economy of the operation of the power system. However, attaining the desired point forecasting accuracy has been regarded as a challenge because of the intrinsic complexity and instability of the power load. Considering the difficulties of accurate point forecasting, interval prediction is able to tolerate increased uncertainty and provide more information for practical operation decisions. In this study, a novel hybrid system for short-term load forecasting (STLF) is proposed by integrating a data preprocessing module, a multi-objective optimization module, and an interval prediction module. In this system, the training process is performed by maximizing the coverage probability and by minimizing the forecasting interval width at the same time. To verify the performance of the proposed hybrid system, half-hourly load data are set as illustrative cases and two experiments are carried out in four states with four quarters in Australia. The simulation results verified the superiority of the proposed technique and the effects of the submodules were analyzed by comparing the outcomes with those of benchmark models. Furthermore, it is proved that the proposed hybrid system is valuable in improving power grid management.

The combined method for interval forecasting (CMIF) is proposed for improved real-time prediction of wind speed uncertainty to facilitate wind turbine operation and power grid dispatching. Time-varying filtering for empirical mode decomposition and phase space reconstruction are used to decompose and reconstruct the original wind speed sequence to solve chaotic phenomena and eliminate noise. Statistical and machine learning models are considered as candidates, and models with excellent performances are selected. Finally, the selected models are combined by a multi-objective optimizer to obtain the final prediction. Experiments were performed using data from the Gansu wind tower, and the results showed that CMIF improved the accuracy of the predicted wind speed interval by 1.07–55.37% compared with single models. The prediction interval had a narrow width while maintaining a high coverage rate, which facilitated accurate quantification of the wind speed uncertainty.

Objectives The study aimed to investigate the causal relationships of gut microbiota (GM), ovarian cancer (OC), endometrial cancer (EC), and potential metabolite mediators using Mendelian randomization (MR) analysis. Methods Bidirectional two-sample MR analysis and reverse MR analysis of GM on OC/EC were employed to determine the causal effects of GM on OC/EC and the mediating role of blood metabolites in the relationship between GM and OC/EC, with results validated through sensitivity analysis. Results We identified 6 pathogenic bacterial taxa associated with OC, including Euryarchaeota , Escherichia-Shigella , FamilyXIIIAD3011group , Prevotella9 , and two unknown genera. Christensenellaceae R.7group , Tyzzerella3 , and Victivallaceae were found to be protective against OC. The increase in EC risk was positively associated with Erysipelotrichia , Erysipelotrichaceae , Erysipelotrichales , and FamilyXI . Dorea , RuminococcaceaeUCG014 , and Turicibacter exhibited a negative correlation with the EC risk. A total of 26 and 19 blood metabolites related to GM were identified, showing significant correlations with OC and EC, respectively. Cytosine was found to be an intermediate metabolite greatly associated with EC and FamilyXI . In reverse MR analysis, the FamilyXIIIAD3011group exhibited a significant bidirectional causal relationship with OC. Conclusion Our study revealed causal relationships of GM and intermediate metabolites with OC/EC, providing new avenues for understanding OC/EC and developing effective treatment strategies.

Dissecting complex quantitative traits is constrained by limited genetic diversity in biparental populations and population structure confounding in genome-wide association studies. Multi-parent Advanced Generation Inter-Cross (MAGIC) populations address these limitations by intercrossing multiple diverse founders followed by selfing to generate immortalized recombinant inbred lines exhibiting extensive recombination and balanced allele frequencies. MAGIC populations synergistically combine high mapping resolution with broad genetic diversity, enabling detection of small-effect QTLs, epistatic interactions, and genotype-by-environment effects. Despite their immense potential and successful deployment across diverse crops, several critical challenges remain regarding founder selection strategies, computational efficiency of haplotype reconstruction, and seamless integration into existing breeding pipeline. In this review, we synthesize current knowledge of MAGIC construction principles, crossing designs, and inbreeding strategies, and critically evaluate genotyping technologies and statistical frameworks including hidden Markov models, identity-by-descent mapping, and multi-locus mixed models. Furthermore, we explored how integrating with high-throughput phenotyping enhances multi-environment trait characterization, with applications across diverse crops revealing common bottlenecks and successful strategies. We also outlined transformative opportunities through joint linkage-association analysis for causal variant identification, integrating MAGIC Populations with AI-driven genomic selection for accelerated genetic gain, and multi-omics approaches for mechanistic trait dissection. This synthesis provides actionable frameworks for optimizing MAGIC population development and exploitation, advancing precision crop improvement in the face of climate change and resource constraints.

Objective To assess inflammation, endothelial damage, and platelet activation during platelet transfusion refractoriness (PTR) in pediatric patients with solid tumors. Methods A cohort of 36 PTR and 38 Non-PTR pediatric patients with solid tumor was enrolled. Patients received standard chemotherapy and platelet transfusion according to guidelines. Levels of inflammatory mediators (IL-1β and IL-8, etc.), endothelial damage marker (vWF), and platelet activation markers (sP-selectin, sCD40L and RANTES) in pre-transfusion plasma were quantified by flow cytometry and ELISA. Associations with PTR, bleeding events, and progression-free survival (PFS) were analyzed by multivariable regression and Cox models. Results The PTR group showed significantly high levels of sP-selectin (14.1 vs. 6.0 ng/mL), sCD40L (293.4 vs. 206.2 pg/mL), vWF (231.7 vs. 162.3 µg/mL), IL-1β (67.4 vs. 38.9 pg/mL), and IL-8 (61.0 vs. 29.2 pg/mL). Multivariable analysis identified vWF (OR = 1.006), IL-1β (OR = 1.013), and IL-8 (OR = 1.021) as independent predictors of PTR. Predictive model combining these three markers with malignancy risk stratification significantly improved the predictive ability of PTR compared to clinical Model alone (AUC: 0.846 vs. 0.692, P  = 0.003). Clinically, PTR patients had delayed platelet recovery (10.2 vs.7.3 days), higher bleeding (36.1% vs. 13.2%), and reduced 500-day PFS (41.5% vs. 55.2%). Elevated sP-selectin (≥ 10.1 ng/mL) and sCD40L (≥ 234.5 pg/mL) predicted bleeding. After adjustment for malignancy risk stratification, high sCD40L (HR = 3.853, 95% CI: 1.097–13.525) remained independently associated with lower PFS, whereas IL ‑ 8 showed a trend but was not statistically significant. Conclusion Elevated IL-8 and sCD40L are novel predictors of PTR and survival prognostic in pediatric patients with solid tumors undergoing chemotherapy. IL-1β, IL-8 and vWF are identified as independent risk factors for PTR. sP-selectin and sCD40L are associated with increased bleeding risk, and high sCD40L is independent predictors of lower 500-day PFS.

The mixed-mode loading fretting fatigue caused by the complex geometry of components and combinations of boundary conditions is a common failure mechanism in engineering components, which can dramatically reduce fatigue life. In this paper, a cylinder-on-flat numerical model was established to investigate tension–bending mixed-mode fretting fatigue. The finite element method in conjunction with two criteria, plane parameters McDiarmid (MD) and Smith–Watson–Topper (SWT), were used to evaluate the effects of mode angle, oblique loading, and stiffness ratio on the contact width, the maximum equivalent stress of the specimen, the surface stress, the fretting damage initiation location, and the extent of the damage initiation. The results indicate that the extent of fretting damage increases with the mode angle, and the characterization parameters are sensitive to smaller mode angles. The contact width, peak surface stress, maximum damage parameters, and damage initiation location can be effectively adjusted by the stiffness ratio. The findings may provide insights into fretting fatigue behavior under complex loading conditions, potentially contributing to enhanced structural safety and reliability for tension–bending mixed-mode loading.

Based on Ctrip’s ‘tourism digital footprint’, the spatial pattern of tourism flows in the Chengdu–Chongqing Economic Circle from 2018 to 2021 is explored, social network analysis and spatial visualisation of tourism information data are conducted, and factors affecting the network structure of tourism flows are analysed using linear weighted regression methods. The results show that tourism flows in the Chengdu–Chongqing Economic Circle show a significant ‘dual core’ polarisation effect. At the end of 2019, as a turning point, the density value of the tourism flow network shows an irregular inverted ‘U’ distribution. Kuanzhai Alley, Hong Ya Dong and Chunxi Road have irreplaceable competitive advantages in the tourism flow network. The density of highways, the number of star-rated hotels and the regional GDP per capita are positively correlated with the effective size of the structural hole of the administrative unit. Finally, based on the research results, countermeasures are proposed to optimise the tourism development of the Chengdu–Chongqing Economic Circle.

Eosinophilic pneumonia (EP) is a rare but noteworthy adverse effect linked to dupilumab, an interleukin-4 (IL-4) and IL-13 inhibitor used in the managing atopic diseases. The underlying mechanisms, potential predisposing factors, clinical characteristics, and optimal management strategies for dupilumab-induced EP remain unclear. We report a 71-year-old patient who developed acute EP after the first 600-mg dose of dupilumab. Eosinophils (EOSs) were also transiently increased (up to 1,600 cells/μl). After the acute EP was effectively treated with glucocorticoids, dupilumab treatment was continued. Rash, itching, and immunoglobulin E levels continued to decrease in the patient, and no further pulmonary adverse events occurred. We combined this case with a literature review of nine articles and analyzed data from 93 cases reported in the FDA Adverse Event Reporting System (FAERS) database of patients developing EP after dupilumab use. Our findings imply that dupilumab may induce EP, particularly in individuals over 45 years old, those with a history of respiratory diseases, and those who have previously used inhaled or systemic steroids. Vigilance is required, especially when there is a persistent elevation in peripheral blood EOSs during treatment. Although steroid treatment can effectively manage EP, more data are needed to determine the safety of resuming dupilumab treatment after controlling pneumonia.

A mutation in VRC01, a broadly neutralizing, HIV-1-specific antibody, confers enhanced binding to the neonatal Fc receptor, increasing the antibody half-life in the serum and localization in mucosal tissues, where it provides superior protection against rectal simian HIV-1 infection in macaques. Enhanced anti-HIV activity in mutant VRC01 antibody The recent discovery of broad and potent anti-HIV-1 antibodies has renewed interest in their use for passive protection against human immunodeficiency virus-1 in humans. This paper describes a mutation in the HIV-specific broadly neutralizing antibody VRC01 that confers enhanced binding to the neonatal Fc receptor and increases the antibody half-life in serum and mucosal tissues. It conferred superior protection in a rectal simian-HIV challenge model in macaques when compared to wild-type VRC01. To protect against human immunodeficiency virus (HIV-1) infection, broadly neutralizing antibodies (bnAbs) must be active at the portals of viral entry in the gastrointestinal or cervicovaginal tracts. The localization and persistence of antibodies at these sites is influenced by the neonatal Fc receptor (FcRn) 1 , 2 , whose role in protecting against infection in vivo has not been defined. Here, we show that a bnAb with enhanced FcRn binding has increased gut mucosal tissue localization, which improves protection against lentiviral infection in non-human primates. A bnAb directed to the CD4-binding site of the HIV-1 envelope (Env) protein (denoted VRC01) 3 was modified by site-directed mutagenesis to increase its binding affinity for FcRn. This enhanced FcRn-binding mutant bnAb, denoted VRC01-LS, displayed increased transcytosis across human FcRn-expressing cellular monolayers in vitro while retaining FcγRIIIa binding and function, including antibody-dependent cell-mediated cytotoxicity (ADCC) activity, at levels similar to VRC01 (the wild type). VRC01-LS had a threefold longer serum half-life than VRC01 in non-human primates and persisted in the rectal mucosa even when it was no longer detectable in the serum. Notably, VRC01-LS mediated protection superior to that afforded by VRC01 against intrarectal infection with simian–human immunodeficiency virus (SHIV). These findings suggest that modification of FcRn binding provides a mechanism not only to increase serum half-life but also to enhance mucosal localization that confers immune protection. Mutations that enhance FcRn function could therefore increase the potency and durability of passive immunization strategies to prevent HIV-1 infection.