Balancing the Binding of Intermediates Enhances Alkaline Hydrogen Oxidation on D-Band Center Modulated Pd Sites.

Exploring efficient alkaline hydrogen oxidation reaction (HOR) electrocatalysts is of great concern for constructing anion exchange membrane fuel cells (AEMFCs). Herein, d-band center modulated PdCo alloys with ultralow Pd content anchored onto the defective carbon support (abbreviated as PdCo/NC hereafter) are proposed as highly efficient HOR catalyst. The as-prepared catalyst exhibits exceptional HOR performance compared to the Pt/C catalyst, achieving thermodynamically spontaneous and kinetically preferential reactions. Specifically, the resultant PdCo/NC demonstrates a marked enhancement in alkaline HOR performance, with the highest mass and specific activities of 1919.6 mA mgPd-1 and 1.9 mA cm-2, 51.1 and 4.2 times higher than those of benchmark of Pt/C, along with an excellent stability in a chronoamperometry test. In the analysis of in situ Raman spectra, it was discovered that tetrahedrally coordinated H-bonded water molecules were formed during the HOR process. This indicates that the promotion of interfacial water molecule formation and enhancement of HOR activities in PdCo/NC are facilitated by defect engineering and the turning of d-band center in PdCo alloy. The essential knowledge obtained in this study could open up a new direction for modifying the electronic structure of cost-effective HOR catalysts through electronic structure engineering.

Manipulation of Electronic States of Pt Sites via d-Band Center Tuning for Enhanced Oxygen Reduction Reaction in Proton Exchange Membrane Fuel Cells.

Expediting the torpid kinetics of the oxygen reduction reaction (ORR) at the cathode with minimal amounts of Pt under acidic conditions plays a significant role in the development of proton exchange membrane fuel cells (PEMFCs). Herein, a novel Pt-N-C system consisting of Pt single atoms and nanoparticles anchored onto the defective carbon nanofibers is proposed as a highly active ORR catalyst (denoted as Pt-N-C). Detailed characterizations together with theoretical simulations illustrate that the strong coupling effect between different Pt sites can enrich the electron density of Pt sites, modify the d-band electronic environments, and optimize the oxygen intermediate adsorption energies, ultimately leading to significantly enhanced ORR performance. Specifically, the as-designed Pt-N-C demonstrates exceptional ORR properties with a high half-wave potential of 0.84 V. Moreover, the mass activity of Pt-N-C reaches 193.8 mA gPt-1 at 0.9 V versus RHE, which is 8-fold greater than that of Pt/C, highlighting the enormously improved electrochemical properties. More impressively, when integrated into a membrane electrode assembly as cathode in an air-fed PEMFC, Pt-N-C achieved a higher maximum power density (655.1 mW cm-2) as compared to Pt/C-based batteries (376.25 mW cm-2), hinting at the practical application of Pt-N-C in PEMFCs.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Laser ultrasonic nondestructive evaluation of sub-millimeter-level crack growth in the rail foot weld.

Laser-generated ultrasonic wave characteristics in the rail foot weld were simulated and reported for qualitative analysis and evaluation of sub-millimeter-level crack growth. Numerical analyses using the finite element method (FEM), the propagation characteristics, and displacement field distribution of a laser-generated ultrasonic wave after the interaction with cracks were fully demonstrated. By calculating displacement amplitude distribution, the optimal sensing position and area were the laser incident point and the upper surface, respectively. Crack growth degree toward the rail bottom and axial direction can be confirmed by analyzing time and amplitude of the echoes originating from the rail bottom and crack surface reflection. By combining time with peak intensity of the echo reflection from the rail bottom, the sub-millimeter-level crack growth process inside the rail foot weld is capable of acquiring and evaluating. The results justify that the laser ultrasonic technique, characterized by laser excitation and laser detection, is a competitive nondestructive testing technique for sub-millimeter-level crack growth evaluation and detection inside the rail foot weld.

Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the most fatal malignancies. Surgical resection supplemented by chemotherapy remains the major therapeutic regimen, but with unavoidable resistance and systemic toxic reaction. Curcumin is a known safe natural compound that can effectively eliminate pancreatic adenocarcinoma cells in vitro, making it a promising candidate for substitution in subsequent chemotherapy. However, due to its extremely low bioavailability caused by its insolubility and circular elimination, curcumin had an unexpectedly modest therapeutic effect in clinical trials. RESULTS: Here, we electrospun curcumin/gelatin-blended nanofibrous mat to largely improve curcumin's bioavailability by local controlled-release. With characterization by scanning electron microscopy, fluorescence microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and high-performance liquid chromatography, it was revealed that curcumin was uniformly dispersed in the fiber of the mats with nanoscopic dimensions and could be continuously released into the surrounding medium for days. The cancer inhibitory effects of nano-curcumin and underlying mechanisms were further explored by assays using pancreatic adenocarcinoma cell and experiments using xenograft model. The results showed the released nano-curcumin could effectively inhibit pancreatic adenocarcinoma cell proliferation not only in vitro, but more importantly in vivo. This cytotoxic effect of nano-curcumin against pancreatic adenocarcinoma was achieved through provoking the production of intracellular reactive oxygen species and activating endoplasmic reticulum stress, which leads to enhanced cell apoptosis via decreased phosphorylation of signal transducer and activator of transcription 3. CONCLUSIONS: Clinically, curcumin/gelatin-blended nanofibrous mat could be a promising, secure, efficient and affordable substitutional agent for the elimination of residual cancer cells after tumor resection. Moreover, our strategy to obtain curcumin released from nanofibrous mat may provide a universally applicable approach for the study of the therapeutic effects and molecular mechanisms of other potential medicines with low bioavailability.

Recombinant Adenoviruses Displaying Matrix 2 Ectodomain Epitopes on Their Fiber Proteins as Universal Influenza Vaccines.

Influenza is a zoonotic disease that poses severe threats to public health and the global economy. Reemerging influenza pandemics highlight the demand for universal influenza vaccines. We developed a novel virus platform using extracellular domain IV of the matrix 2 protein (M2e), AdC68-F3M2e, by introducing three conserved M2e epitopes into the HI loop of the chimpanzee adenovirus (AdV) fiber protein. The M2e epitopes were expressed sufficiently on the AdV virion surface without affecting fiber trimerization. Additionally, one recombinant adenovirus, AdC68-F3M2e(H1-H5-H7), induced robust M2e-specific antibody responses in BALB/c mice after two sequential vaccinations and conferred efficient protection against homologous and heterologous influenza virus (IV) challenges. We found that the use of AdV with tandem M2e epitopes in fiber is a potential strategy for influenza prevention.IMPORTANCE Influenza epidemics and pandemics severely threaten public health. Universal influenza vaccines have increasingly attracted interest in recent years. Here, we describe a new strategy that incorporates triple M2e epitopes into the fiber protein of chimpanzee adenovirus 68. We optimized the process of inserting foreign genes into the AdC68 structural protein by one-step isothermal assembly and demonstrated that this 225-bp HI loop insertion could be well tolerated. Furthermore, two doses of adjuvant-free fiber-modified AdC68 could confer sufficient protection against homologous and heterologous influenza virus infections in mice. Our results show that AdC68-F3M2e could be pursued as a novel universal influenza vaccine.

Modified Unilateral Pedicled V-Y Advancement Flap for Scalp Defect Repair.

Reconstruction of scalp defects caused by tumor resection or trauma is very challenging. A majority of the surgeons prefer to use local flap rather than skin graft or free flap for scalp defects repair. The aim of this study is to investigate the technique of modified unilateral pedicled V-Y advancement flap for the reconstruction of scalp defect.A retrospective review was performed in a series of 18 patients who had a modified unilateral pedicled V-Y advancement flap to restore scalp defect from May 2013 to January 2017. Their mean age is 58 (24-78) years. These patients suffered from basal cell carcinoma, seborrhoeic keratosis, squamous cell carcinoma, or trauma on the scalp. All of them underwent preoperative Doppler scanning to identify the scalp arteries and then individually designed. The flap size ranged from 33 × 50 mm to 68 × 105 mm. Patients were followed for an average of 12 months postoperatively (ranged from 6 to 37 months). No major complications occurred, only 2 cases had a minor distal epidermal necrosis or obstruction of venous backflow observed for the first 3 days of the surgery, and they both healed well. Modified unilateral pedicled V-Y flap technique with fairly rapid recovery and acceptable reorientation of hair follicles leads to esthetical outcome and patient satisfaction. Most importantly, no tumor recurrence at the original site during the follow-up period was seen.The modified unilateral pedicled V-Y advancement flap is a simple but efficient technique, particularly suitable for the repair of small and medium size scalp defects with advantages including the safety of the procedure and overall esthetic results like hairline preservation and less scarring when compared to other local flap techniques.

The Distally Based Sural Flap for the Reconstruction of Ankle and Foot Defects in Pediatric Patients.

BACKGROUND: Skin and soft tissue defects at the level of the ankle and the heel remain a great challenge for plastic and reconstructive surgeons. There were just a few reports on the use of distal-based sural flap in pediatric patients. The purpose of this study was to introduce our experience in the treatment of skin and soft tissue defects of the pediatric feet by using this distally based sural neurocutaneous flap together with some technical modifications for a large-sized defect. METHODS: From July 2004 to October 2012, a total of 36 children younger than 12 years were treated with distally based sural flap for a variety of soft tissue defects of the foot and the ankle. All patients experienced a traffic accident. Thirty-four patients received standard distal-based reverse sural flaps, and 2 children received the flaps with nerve and vein sparing. RESULTS: The duration of follow-up varied from 3 to 48 months. All flaps survived completely. Two flaps presented vascular insufficiency and resulted in partial distal superficial necrosis (10%-20%). Two children had a compressive ulcer because of improper shoes wearing. There were no complaints related to the killing of the sural nerve. CONCLUSIONS: The distally based sural flap is an excellent choice in pediatric patients for covering defects of the lower leg and the foot because of its simplicity, versatility, low risk, and minimal donor site morbidity.

The John D. Constable International Traveling Fellowship: A Reciprocal Education in Plastic Surgery.

The John D. Constable International Traveling Fellowship has been an integral part of the American Association of Plastic Surgeons since 2006 and has provided an opportunity for international plastic surgeons to work with leaders in American plastic surgery.

Free lateral great toe flap for the reconstruction of finger pulp defects.

INTRODUCTION: The aim of this study was to evaluate the esthetic and sensory outcomes after reconstruction of finger pulp defects with free toe flaps from the lateral aspect of the great toe. METHODS: From June 2006 to October 2011, we performed 48 free toe pulp transfers for finger pulp reconstruction in 43 patients; 18 male and 25 female patients with a mean age of 31.8 years (range, 16-47 years). Six patients suffered multiple digital pulp defects and five received two synchronous pulp transfers. The defects involved 20 thumbs, 15 index fingers, 10 long fingers, and 4 ring fingers, and flap size ranged from 24 × 18 to 55 × 30 mm. Follow-up evaluation included the functional and esthetic outcomes of the reconstructed pulps and donor toes. RESULTS: All but one flap survived completely. Overall, 32 cases (35 pulp flaps) were followed for more than 1 year (range, 12-48 months; average, 22.8 months). The Semmes-Weinstein sensitivity score was 2.83 to 4.74 at the flaps and the mean static two-point discrimination was 6.17 mm (range, 3-10 mm). A total of 13 patients (40.6%) experienced mild (10 cases) to moderate (3 cases) cold intolerance, and 1 patient (3.1%) suffered severe cold intolerance. According to the Michigan Hand Outcome Questionnaire the mean esthetic appearance score was 16 (range, 12-19). CONCLUSION: The free neurovascular great toe pulp flap is an efficient and reliable flap for the reconstruction of finger pulp defects.

Extended reverse dorsal metacarpal artery flap for coverage of finger defects distal to the proximal interphalangeal joint.

UNLABELLED: Finger reconstruction distal to the proximal interphalangeal (PIP) joint is a challenging task for hand surgeons. Although extended reverse dorsal metacarpal artery (RDMA) flaps were described for coverage of finger defects, reports on repairs beyond the PIP joint are limited. The occurrence of venous congestion of the flaps and their treatments require further clarification. METHODS: Extended RDMA flaps were used to cover the finger defects extending from the PIP joints to the fingertips in a series of 16 patients. The reconstructed fingers included the index, middle, ring, and little fingers; thumb reconstruction was not included in this study. The flap size ranged from 2.5×1.8 to 5×3 cm. A composite flap with a segment of tendon was applied for a complex reconstruction in 4 cases. Either superficial branch of radial nerve or dorsal branch of ulnar nerve was included in flap elevation because of its perineural vascular network contributing to the flap perfusion. The pivot point was located at the level of the middle point of the proximal phalanx, where the communicating branches between the proper palmar digital artery and the dorsal metacarpal artery exist. A teardrop skin pedicle was used to reduce the tension of the flap pedicle. RESULTS: All flaps totally survived except that 1 flap had epidermal loss later salvaged by secondary skin grafting. Venous congestion occurred in the distal part of 5 flaps and was effectively relieved after multiple subcutaneous heparin injections. Neither of the 2 cases of nerve repair resulted in significant improvement in sensation. All donor sites were primarily closed. CONCLUSIONS: Extended RDMA flaps can be effectively applied in the reconstruction of finger defects beyond PIP joint. Its advantages include a simple dissection, single-stage reconstruction, and preservation of digital artery and nerve. The donor site can be primarily closed if the flap width is less than 3 cm. Multiple subcutaneous heparin injection is a preferred solution in cases where venous congestion occurs in the flap.

Modified technique for one-stage treatment of proximal phalangeal enchondromas with pathologic fractures.

PURPOSE: To evaluate the treatment outcome for enchondromas of the proximal phalanx with pathological fracture. METHODS: Between June 2008 and October 2012, we treated 9 patients with solitary proximal phalanx enchondromas and pathologic fractures by curetting the tumor, filling the void with a block of autogenous bone chip, and applying a low-profile miniplate. Postoperative follow-up included clinical assessment, pain evaluation, and radiographs. RESULTS: Follow-up time ranged from 13 to 42 months (mean, 30 mo). No major complications such as notable malalignment, nonunion, infection, or tumor recurrence were observed. All fractures healed after a mean of 8 weeks postoperatively. Full motion was achieved in 5 patients and extension lag (5° to 10°) of the proximal interphalangeal joint persisted in 4. Function was excellent in all patients according to the Takigawa criteria. All patients reported they were pain free and had resumed presurgical function within 12 weeks after surgery. CONCLUSIONS: Tumor curettage, reconstruction of the bone defect with a block of autogenous bone chip, and low-profile miniplate fixation provided one-stage treatment with immediate rigid stabilization and good functional outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

A study on mindful agency's influence on college students' engagement with online teaching: The mediating roles of e-learning self-efficacy and self-regulation.

METHODOLOGY: A total of 379 college students from 22 classes in 3 universities in Nanjing, who received online teaching, were selected as the participants in this study. The purpose of this thesis is to explore the influence mechanism of mindful agency on their identification by using the Mindful Agency Scale for College Students, the Scale for Identification of College Students with Online Teaching, the Online Learning Self-Efficacy Scale for Adult Learners, and the Questionnaire on Online Self-Disciplined Learning for College Students, which were proven effective in previous studies. In all these studies, the coefficients of Cronbach's α are all above 85. RESULTS: The study's findings demonstrated that, in addition to directly and favorably predicting identification with online teaching, mindful agency also had an impact on identification through the mediating effects of self-efficacy in online learning and self-disciplined learning online. CONCLUSIONS: By identifying the two intermediary pathways and the orderly chain structure pathways in which mindful agency influences college students' identification with online teaching, this study contributes to the theoretical research on mindfulness in online teaching contexts, the expansion of empirical research on the impact of mindful agency on identification with online teaching, and the development of practical reference materials for improving identification with online teaching.

Preparation of microspheres with sustained ketoprofen release by electrospray for the treatment of aseptic inflammation.

The treatment of aseptic inflammation has always been a clinical challenge. At present, non-steroidal drug-loaded microspheres have been widely used in the treatment of aseptic inflammation due to their excellent injectable and sustained release capabilities. In this study, ketoprofen-loaded shellac microspheres (Keto-SLAC) were prepared by electrospray. Alterations of Keto-SLAC morphology was observed in response to changed shellac concentration in ethanol solution through electrospray. Further examination revealed that ketoprofen presented as amorphous solid dispersion in the shellac microspheres. Most importantly, it was also shown that ketoprofen can be slowly released from the shellac matrix for up to 3 weeks. In vitro cell experiments verified that the microspheres had favorable cell compatibility. We therefore proposed that the prepared microspheres, being readily available in use in a variety of clinical settings through topical application, have promising therapeutic potential for the treatment of aseptic inflammation.

Growth and development and trends in overweight and obesity among 7-12 years old Hmong children in China: an analysis of eight successive national surveys from 1985 to 2019.

Background: To explore the dynamic changes and trends in the body shape of Hmong children aged 7-12 years from 1985 to 2019, and to predict them, to provide a reference for the physical health level of Hmong children. Methods: The body shape data of Hmong children aged 7-12 years old from the Chinese National Survey on Students' Constitution and Health (CNSSCH) in 1985, 1991, 1995, 2000, 2005, 2010, 2014, and 2019 were used for longitudinal comparative analysis, and the grey GM(1,1) model was established based on this as a time series. Forecast the future development trend in 2025 and 2030. Results: 1) From 1985 to 2019, all indicators of body shape of Hmong primary school students showed an upward trend, the increase in height (F Boys = 3.91, p > 0.05; F Girls = 3.91, p > 0.05), weight (F Boys = 8.04, p < 0.01; F Girls = 6.36, p < 0.05) and BMI (F Boys = 19.15, p < 0.01; F Girls = 10.24, p < 0.01) increased with age, rate of growth: Weight > BMI > Height, girls grow faster than boys; 2) The prevalence of overweight and obesity increased year by year, from 5.2 and 1.2% in 1991 to 12.4% (χ2 linear trend = 3.89, p < 0.05) and 8.7% (χ2 linear trend = 3.98, p < 0.05) in 2014, respectively, showing a significant growth trend, especially after 2000, overweight and obesity have entered a stage of rapid growth; 3) The forecast results show that the height, weight and BMI will continue to increase in 2025 and 2030, but the growth rate will decrease, the increase of weight and BMI is greater than the height, overweight and obesity are still expected to increase rapidly. Conclusion: The growth and development level of Hmong elementary children continues to increase, and the prevalence of overweight and obesity is increasing year by year, requiring early prevention and intervention to promote the healthy development of physical fitness of Hmong, as well as other ethnic minority students.

Causality of genetically determined blood metabolites on irritable bowel syndrome: A Mendelian randomization study.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders and dysmetabolism plays an important role in the pathogenesis of disease. Nevertheless, there remains a lack of information regarding the causal relationship between circulating metabolites and IBS. A two-sample Mendelian randomization (MR) analysis was conducted in order to evaluate the causal relationship between genetically proxied 486 blood metabolites and IBS. METHODS: A two-sample MR analysis was implemented to assess the causality of blood metabolites on IBS. The study utilized a genome-wide association study (GWAS) to examine 486 metabolites as the exposure variable while employing a GWAS study with 486,601 individuals of European descent as the outcome variable. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of metabolites on IBS, while several methods were performed to eliminate the pleiotropy and heterogeneity. Another GWAS data was used for replication and meta-analysis. In addition, reverse MR and linkage disequilibrium score regression (LDSC) were employed for additional assessment. Multivariable MR analysis was conducted in order to evaluate the direct impact of metabolites on IBS. RESULTS: Three known and two unknown metabolites were identified as being associated with the development of IBS. Higher levels of butyryl carnitine (OR(95%CI):1.10(1.02-1.18),p = 0.009) and tetradecanedioate (OR(95%CI):1.13(1.04-1.23),p = 0.003)increased susceptibility of IBS and higher levels of stearate(18:0)(OR(95%CI):0.72(0.58-0.89),p = 0.003) decreased susceptibility of IBS. CONCLUSION: The metabolites implicated in the pathogenesis of IBS possess potential as biomarkers and hold promise for elucidating the underlying biological mechanisms of this condition.

Enhanced Cycling Performance of Spinel LiNi0.5Mn1.5O4 Cathodes through Mg-Mn Hetero-Valent Doping via Microwave Sol-Gel Method.

As a high energy density cathode material, further development of high working voltage spinel LiNi0.5Mn1.5O4 has hindered by its rapid capacity degradation. To address this, a hetero-valent substitution of magnesium for manganese was used to synthesize spinel LiNi0.5MgxMn1.5-xO4 (x = 0, 0.03, 0.05) via a microwave sol-gel method. XRD and refined results indicate that such strategy leads to the modification of the 16c interstitial sites. The electrical performance demonstrates that a modest substitution (x = 0.03) significantly improves both rate performance (113.1 mAh/g, charge and discharge at 5 C) and cycling stability (85% capacity retention after 500 cycles at 1 C). A higher substitution level (x = 0.05) markedly improves high-rate cycling performance, achieving 96% capacity retention after 500 cycles at 5 C. It offers tailored solutions for various application needs, including capacity-focused and high-current-rate applications. Furthermore, the stable LiNi0.5Mg0.05Mn1.45O4 sample could also serve as an effective coating layer for other electrode materials to enhance their cycling stability.

Advances and challenges in thermal runaway modeling of lithium-ion batteries.

The broader application of lithium-ion batteries (LIBs) is constrained by safety concerns arising from thermal runaway (TR). Accurate prediction of TR is essential to comprehend its underlying mechanisms, expedite battery design, and enhance safety protocols, thereby significantly promoting the safer use of LIBs. The complex, nonlinear nature of LIB systems presents substantial challenges in TR modeling, stemming from the need to address multiscale simulations, multiphysics coupling, and computing efficiency issues. This paper provides an extensive review and outlook on TR modeling technologies, focusing on recent advances, current challenges, and potential future directions. We begin with an overview of the evolutionary processes and underlying mechanisms of TR from multiscale perspectives, laying the foundation for TR modeling. Following a comprehensive understanding of TR phenomena and mechanisms, we introduce a multiphysics coupling model framework to encapsulate these aspects. Within this framework, we detail four fundamental physics modeling approaches: thermal, electrical, mechanical, and fluid dynamic models, highlighting the primary challenges in developing and integrating these models. To address the intrinsic trade-off between computational accuracy and efficiency, we discuss several promising modeling strategies to accelerate TR simulations and explore the role of AI in advancing next-generation TR models. Last, we discuss challenges related to data availability, model scalability, and safety standards and regulations.