Photoelectrochemical (PEC) sensors exhibit significant promise for early disease diagnosis and trace-level biomarkers detection, owing to their exceptional sensitivity, strong anti-interference capacity. Nevertheless, the relatively low photoelectric conversion efficiency remains a limiting factor for their detection performance. In this paper, a high-performance PEC sensing strategy was proposed based on the engineered dual active centers of surface plasmon resonance and oxygen vacancy in the homologous Bi-Bi2O3 Schottky heterojunction structure. With this configuration, the photocurrent response was significantly enhanced by interface band structure regulation. To achieve higher sensitivity in photocathode analysis, a duplex-specific nuclease-assisted cycle strategy was employed to stabilize the photocurrent signal, and AgInS2 quantum dots were used as electron traps to collect photogenerated electrons in Bi-Bi2O3, which resulted in the signal being further amplified. By precisely capturing significant variations in the photocurrent signals, highly sensitive detection of microRNA166a was achieved, with a low detection limit (5.6 pM) and a broad linear detection range (10 pM to1μM). This work established the basis for efficient signal modulation strategies in high-performance PEC sensors.

Diabetic retinopathy (DR) is one of the most prevalent complications of diabetes which could lead to vision impairment. Dysfunction of the retinal pigment epithelium (RPE) is an early pathogenic event, where various mechanisms may contribute to the disease progression. circular RNAs (circRNAs) have been reported to be important regulators in diabetic complications, acting as miRNA sponge, participating in the regulation of gene transcription or coding short peptides. Circular RNA microarray and RNA-seq were used to identify differentially expressed circRNAs in ARPE-19 cells in normal and high glucose treatments. The expression of cKIAA1462, miR-183-5p, and high mobility group box 1 (HMGB1) were determined using quantitative real-time polymerase chain reaction and Western blot. In vitro experiments, such as flow cytometry, Western blot, and Electron microscope (TEM) were conducted. The binding interaction was confirmed using dual-luciferase reporter and overexpression/inhibition experiments. cKIAA1462 was knocked down via intravitreal lentiviral injection in diabetic mice, followed by expression level detection, functional analysis and histological assessments. cKIAA1462 was significantly upregulated under high glucose conditions both in vitro and in vivo (in retinas of diabetic mice). It acted as a molecular sponge for miR-183-5p, increasing the expression of HMGB1. Elevated HMGB1 concurrently impaired autophagic flux (increased p62, decreased autophagosomes) and activated the NLRP3 inflammasome (upregulated NLRP3, ASC, caspase-1), promoting pyroptosis. Silencing cKIAA1462 in vivo restored autophagy, suppressed pyroptosis, improved retinal structure, and enhanced electroretinogram responses in diabetic mice. The cKIAA1462/miR-183-5p/HMGB1 axis plays a critical role in diabetic RPE injury by dual regulation of autophagy and pyroptosis. Targeting this pathway may offer a novel therapeutic strategy for early diabetic retinopathy.

To assess the efficacy and acceptability of non-pharmacological therapies, novel pharmaceuticals, and their combination for autism and explore the preferred treatment options for autism. A thorough search was conducted across PubMed, Web of Science, The Cochrane Library, Embase, PsycINFO, China National Knowledge Infrastructure, and Medline databases to collect all studies associated with randomized controlled trials on non-pharmacological or new pharmacological interventions for autism, up to October 2024. Two researchers will independently conduct literature screening, data extraction, and quality assessment. The primary outcome will be assessed by the severity of core autistic symptoms using validated scales and standardized mean differences (SMDs). In contrast, the secondary outcome will focus on the acceptability of the treatment. We performed a network meta-analysis within a frequentist framework, utilizing the network package in statistical software Stata 18. 106 RCTs were involved, including 5986 patients, and data from 21 interventions were analyzed. Compared with placebo, the following interventions improved the core symptoms of autism: exercise (SMD = -1.05, 95

PURPOSE:To evaluate the individual and combined diagnostic performance of cytokine, molecular, and clonality biomarkers for primary vitreoretinal lymphoma (PVRL). DESIGN:Systematic review and meta-analysis. PARTICIPANTS:A total of 2411 patients from 41 studies with confirmed PVRL or benign ocular inflammatory diseases. METHODS:Prospectively registered (CRD420251265910). Four databases were searched through November 25, 2025. Methodologic quality was assessed using QUADAS-2 and Comparative tools. Diagnostic accuracy was pooled using hierarchical summary receiver operating characteristic (HSROC) models with GRADE certainty assessment. MAIN OUTCOME MEASURES:Pooled sensitivity, specificity, and AUSROC for each biomarker with GRADE certainty ratings. RESULTS:Of 41 included studies, most were rated at high or unclear risk of bias across Quality Assessment of Diagnostic Accuracy Studies 2 domains, predominantly in patient selection because of retrospective designs and nonconsecutive sampling, and in the index test domain because of post hoc threshold selection. The interleukin (IL)-10 to IL-6 ratio (27 studies; 1370 patients; AUSROC, 0.98; sensitivity, 0.89; specificity, 0.98; I2 = 61% and 69%, respectively; low certainty) showed no publication bias. MYD88 (12 studies; 382 patients; AUSROC, 0.89; sensitivity, 0.73, specificity, 0.99; I2 = 37% and 68%, respectively; very low certainty), IGH (12 studies; 649 patients; AUSROC, 0.97; sensitivity, 0.85, specificity, 0.97; I2 = 80% and 87%, respectively; very low certainty), and IL-10 alone (11 studies; 549 patients; AUSROC, 0.94; sensitivity, 0.87, specificity, 0.95; I2 = 58% and 84%, respectively; low certainty) did not outperform IL-10 and IL-6 statistically. CD79B (4 studies; 123 patients; AUSROC, 1.00; sensitivity, 0.40; specificity, 1.00; I2 = 35% and 0%, respectively; low certainty) showed numerically higher accuracy (P = 0.055). Parallel testing of IL-10 to IL-6 ratio and MYD88 achieved 97.1% sensitivity and 97.0% specificity, reducing false-negative rates from 11% to 2.9%. CONCLUSIONS:Parallel testing of IL-10 to IL-6 ratio and MYD88 seemed to offer the highest diagnostic performance among evaluated strategies for PVRL, although this finding requires prospective validation given the low to very low certainty of the underlying evidence. Aqueous humor cytokine testing yielded higher diagnostic odds ratios than vitreous fluid, suggesting anterior paracentesis for IL-10 to IL-6 ratio before vitreous biopsy for molecular confirmation. FINANCIAL DISCLOSURE(S):The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The emerging antifungal resistance exacts deteriorating effects on the availability of drugs for treating fungal infections, calling for novel therapies. Although amphotericin B (AmB) is clinically effective and rarely causes resistance, its severe side effects warrant further reduction. Enhancing or potentiating AmB efficacy with other agents to lower the dose of AmB is appealing to reduce AmB toxicity. Dioscin, a steroidal saponin from the Dioscorea genus, has shown multiple pharmacological activities, including anticancer, antifungal, hepatoprotective, and nephroprotective effects. As combinational therapy has multiple advantages, it is interesting to explore the effects of dioscin and AmB combination in C. albicans, which is the most common fungal pathogen in humans. In this study, through a checkerboard assay, we found that dioscin and AmB produced synergistic effects in inhibiting the planktonic growth of C. albicans, Candida krusei, and Candida tropicalis at 24 h. Dioscin (1 μg/mL) and AmB (0.625 μg/mL) synergistically inhibited the biofilm formation (97%) and development (60%) of C. albicans (SC5314), significantly superior to either agent alone (p < 0.01). Time-killing assay revealed that the combination of dioscin (1 μg/mL) and AmB (0.625 μg/mL) greatly enhanced the killing efficacy compared to either agent alone. The hyphal formation and adhesion to abiotic surfaces of C. albicans were also suppressed by this combination. The damages to the cell membrane caused by this combination were revealed by the cell membrane integrity assay and cell membrane potential assay using fluorescent dyes. Cell membrane damage was further confirmed by results from the transmission electron microscope and scanning electron microscope. Overall, our results suggested that the synergistic combination of dioscin and AmB causes cell membrane damage and holds great potential for future development as anti-Candida therapies.

Objective: This study aims to create a prognostic nomogram by combining clinicopathologic variables that are linked to the overall survival following the surgical removal of esophageal squamous cell carcinoma. Methods: A total of 224 patients with esophageal cancer who underwent surgical R0 resection were included. The construction of the nomogram involved using a multivariable Cox proportional hazards regression model. To evaluate the model's effectiveness, Kaplan-Meier curves and calibration plots were used for discrimination and calibration, respectively. Results: Nearly half of the patients were >60 years old (45.1%), and 95.5% of the patients were male. After esophageal cancer resection, 35.7% of patients experienced complications, with 23.7% developing anastomotic stenosis and 4.5% developing a fistula. Using the backward selection of clinically relevant variables, we found that tumor located in middle thoracic (hazard ratio 2.299, 95% confidence interval 1.008-5.244), anastomotic fistula (3.028, 1.436-6.384), and vascular invasion (2.175, 1.496-3.108) were independently associated with mortality (all P < .05), whereas lymph node clearance >15 nodes is associated with longer survival (0.444, 0.278-0.710) (P = .001). On the basis of these factors, a nomogram was created to predict survival of esophageal squamous cell carcinoma after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.673). Conclusions: A nomogram was created based on the experience from northeast China to forecast overall survival following resection for esophageal squamous cell carcinoma. The validation process demonstrated accurate distinction and calibration, indicating the practical value of the nomogram in enhancing personalized survival predictions for patients who undergo esophageal squamous cell carcinoma resection in this study population. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:To develop a deep learning-based model that is capable of automatically segmenting teeth in cone-beam computed tomography (CBCT) images and generating auxiliary diagnostic reports. METHODS:A two-stage pipeline model comprising a segmentation module and a classification module was designed. The segmentation module integrates the 3D TransUNet model and fine-tuned nnU-Netv2 framework to predict tooth location and numbering. The classification module uses a 3D DenseNet169 model to assess tooth conditions and detect dental diseases. A total of 450 CBCT datasets were collected, preprocessed, and annotated with tooth contours, numbering, and disease status. The dataset was randomly split into training, validation, and test sets at a 3:1:1 ratio. The model's performance was then evaluated by using multiple quantitative metrics. RESULTS:The segmentation module achieved a Dice similarity coefficient (DSC) of 0.9409 and an average symmetric surface distance (ASSD) of 0.5011. The classification module, which is based on the 3D DenseNet169 model, achieved an accuracy of 0.9297 and an F1-score of 0.9252. CONCLUSIONS:The two-stage pipeline model effectively integrates automated tooth segmentation and auxiliary diagnosis. The segmentation module demonstrates high accuracy, while the classification module exhibits strong diagnostic performance. The final output seamlessly combines segmentation and the diagnostic results, enabling the automated generation of structured auxiliary diagnostic reports with tooth numbering. By significantly enhancing the diagnostic efficiency, the proposed method offers substantial support for clinical decision-making in dentistry and holds great potential for real-world applications.

Background/Objectives: The elimination of bacterial biofilm formation is an effective strategy against bacterial infections. The objective was to design 27 colchicine C-ring modified amine derivatives and evaluate their inhibitory activities against the biofilms of MRSA USA300. Methods: Design 27 colchicine C-ring modified amine derivatives. Evaluate their inhibitory activities against MRSA USA300 biofilms. Conduct antibacterial or synergistic antibacterial experiments. Research the phenotypic mechanisms related to biofilm-related genes icaA and agrA. Results: The experiments showed that most compounds in this series exhibited varying degrees of biofilm inhibitory activity (with inhibition rates ranging from 7.72% to 40.79%). Further verification through antibacterial or synergistic antibacterial experiments revealed that the compounds with biofilm-inhibiting effects (compounds 7b–11b) generally had certain antibacterial activities (MICs = 16–32 μg/mL) or synergistic antibacterial effects (FICIs < 0.5). Furthermore, through in-depth research on their phenotypic mechanisms (i.e., research on biofilm-related mechanisms), it was found that the compounds with antibacterial or synergistic antibacterial properties could inhibit the formation of biofilms by affecting the regulation of the biofilm-related genes icaA and agrA. Conclusions: The designed colchicine C-ring modified amine derivatives showed potential in inhibiting MRSA biofilms, and their antibacterial or synergistic antibacterial properties are related to the regulation of biofilm-related genes icaA and agrA, demonstrating inhibitory activity against MRSA.

BACKGROUND:This study aimed to evaluate the diagnostic value of special AT-rich sequence binding protein 2 (SATB2) in distinguishing between osteogenic tumors and non-osteogenic tumors, providing reliable scientific evidence for its use as an adjunct diagnostic tool in clinical practice. METHODS:We conducted systematic searches of the PubMed, EMBASE, Cochrane Library, and Web of Science databases to identify all relevant literature published up to June 2025 that studied SATB2 in the differential diagnosis between osteogenic and non-osteogenic tumors. The QUADAS-2 tool was used to evaluate the methodological quality of each included study. Meta-analysis was performed using STATA SE-64 and RevMan 5.4 software. RESULTS:10 studies involving a total of 1234 cases were included, comprising 494 patients with osteogenic tumors and 740 patients with non-osteogenic tumors. The pooled sensitivity and specificity of SATB2 for differentiating osteogenic from non-osteogenic tumors were 0.97 (95 % CI: 0.90-0.99) and 0.88 (95 % CI: 0.73-0.96), respectively. The PLR was 8.17 (95 % CI: 3.30-20.23), and the NLR was 0.03 (95 % CI: 0.01-0.12). The DOR was 252.82 (95 % CI: 41.85-1527.16). The AUC was 0.98 (95 % CI: 0.97-0.99). CONCLUSION:SATB2 demonstrates high sensitivity and robust specificity as an adjunct diagnostic marker for differentiating osteogenic from non-osteogenic tumors. However, it should be noted that this study excluded tumors with ambiguous definitions, such as giant cell tumors of bone. Future research should further validate the clinical utility of SATB2 in these and other challenging lesions.

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA), a principal causative agent of infections worldwide, urgently requires innovative interventions to counter its increasing risk. The present study revealed the profound impact of farrerol (FA), a robust bioactive agent, on the virulence and resistance mechanisms of MRSA. Our in-depth investigation revealed that FA significantly mitigated the β-lactam resistance of MRSA USA300, an achievement attributed to its precise interference with the BlaZ and Pbp2a protein. Additionally, FA indirectly diminishes the oligomerization of PBP2a by disrupting pigment synthesis, further contributing to its efficacy. In addition, FA extends its functional footprint beyond resistance modulation, exhibiting substantial antivirulence efficacy through selective inhibition of the accessory gene regulator (Agr) system, thereby significantly curbing MRSA pathogenicity in A549 cell and murine models. This study comprehensively explored the multiple impacts of FA on MRSA, shedding light on its versatile role as a BlaZ suppressor, pigment synthesis regulator, and AgrA activity modulator. These intricate findings firmly position FA as a compelling therapeutic candidate for addressing MRSA infections in the clinic.

Organic cocrystals have garnered significant research attention owing to their distinctive properties and promising applications. However, challenges in molecular structure design and control of intermolecular interactions continue to impede further advancements. In this study, two novel cocrystals were successfully formed from a series of synthesized benzotriazole derivatives. The resulting cocrystals exhibit bright green and yellow fluorescence under 365 nm light. To elucidate the microstructure of the obtained cocrystals, systematic characterization techniques such as solid-state fluorescence emission spectroscopy, Single-crystal X-ray diffraction (SCXRD), Power X-ray diffraction (PXRD) and density functional theory (DFT) were performed. These benzotriazole-based cocrystals demonstrate distinct fluorescent responses to alkaline and acidic environments, respectively. Additionally, preliminary tests for fingerprint recognition yielded satisfactory results. These findings suggest that the two cocrystals hold potential applications in acid-alkali sensing, anti-counterfeiting labels, and smart material development, while also providing valuable insights for the design and optimization of solid-state luminescent materials.

Background: To evaluate the efficacy of laparoscopic para-aortic lymphadenectomy in the treatment of gynecologic malignancies through a literature review comparing the extraperitoneal and transperitoneal approaches. Methods: A comprehensive computerized search of PubMed, Embase, the Cochrane Library, Medline, Web of Science, and other relevant databases was conducted, covering the period from January 2010 to January 2025, to collect studies that compared the transperitoneal and extraperitoneal approaches to laparoscopic para-aortic lymphadenectomy in the treatment of gynecologic malignancies. Relevant data were extracted and analyzed using the Review Manager (RevMan) version 5.4.1 statistical software. Outcome indexes included operation time, intraoperative blood loss, number of para-aortic lymph nodes dissected, hospitalization days, and incidence of surgical complications. Results: A total of 525 manuscripts were retrieved, of which 8 were included. Our analysis showed no statistically significant differences between the extraperitoneal and transperitoneal groups in terms of operative time, intraoperative bleeding, and hospitalization days. However, the complication rate was significantly lower in the extraperitoneal group than in the transperitoneal group. Additionally, the number of para-aortic lymph nodes (PAL) retrieved was significantly higher in the extraperitoneal group compared to the transperitoneal group [mean difference (MD) = 0.43, 95% confidence intervals (CI) (0.13 to 0.72, p = 0.004)]. Conclusion: Laparoscopic para-aortic lymphadenectomy for gynecologic malignancies offers several advantages when performed via the extraperitoneal route. This approach reduces surgical trauma, shortens hospital stay, lowers the rate of complication, and increases the number of lymph nodes that can be resected compared to the transperitoneal route. Registration: The study has been registered on https://www.crd.york.ac.uk/prospero/ (registration number: CRD420251033897; registration link: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251033897).

The construction of a nanozyme-enzyme hybrid cascade system is an effective protocol to optimize the performance of biosensors. Yet, the integration has limitations due to the lack of harmonious collaboration between nanozyme and enzyme. Herein, we have constructed an efficient enzymatic cascade system by utilizing the base complementary pairing and the targeting capability of DNA tweezers to combine DNA-regulated copper nanoflowers (CuNFs) with acetylcholinesterase (AChE). The DNA tweezers were immobilized onto the CuNFs undergo regular base complementary pairing, and subsequently employed as aptamer to capture AChE gently, forming CuNFs-Apt-AChE cascade system. This system not only enhanced the spatial proximity of CuNFs and AChE to increase cascade catalytic activity, but also demonstrated excellent stability under harsh conditions. Harnessing the nanoarchitecture and characteristics, the CuNFs-Apt-AChE composites were embedded into the hydrogel to fabricate a sensitive biosensor for on-site detecting carbamate pesticides with a detection limit of 0.19 ng mL-1. The hydrogel sensor exhibited high specificity for carbamate pesticides and had been successfully applied in water and juice samples for pesticide detection with strong anti-interference ability. This method holds great potential for the on-site detection of pesticides, offering a new strategy for constructing nanozyme-enzyme cascade hybrid systems with accuracy and sensitivity.

In this paper, a novel coumarin-based fluorescent probe (8-acetyl-3-(2H-benzo[d][1,2,3]triazol-2-yl)-7-((tert-butyldimethylsilyl)oxy)-2H-chromen-2-one, CTA5) was designed and synthesized for monitoring the process of some reaction involving fluoride ions. CTA5 has a strong fluorescent emission peak at 451 nm, and the emission peak is red-shifted to 517 nm after the reaction with fluoride ions and CTA5 has also good selectivity and linear relationship for fluoride ions detection. Furthermore, CTA5 was applied to monitor the change of fluoride ions concentration in some substitution reactions, and the end of the reaction can be judged by the equilibrium of fluoride ion concentration. The experimental results show that it is feasible to use fluorescence signal to monitor the progress of the reaction.

In the original publication [...].

The fungus Candida albicans causes various kinds of human infections, including oral thrush, vulvovaginitis and life-endangering bloodstream infections, the incidence of which are rising. Worsening this, the clinical antifungals are limited to a few, highlighting the necessity to develop novel antifungal therapies. In this study, the antifungal activities of isobavachalcone against C. albicans SC5314 and nine C. albicans clinical isolates were tested. The effects of isobavachalcone (IBC) on C. albicans virulence factors, such as hyphal formation, adhesion, biofilm formation and extracellular phospholipase production, as well as the underlying mechanism, were also evaluated. Antifungal susceptibility test revealed that IBC has significant anti-Candida activities, with both MIC and MFC being 4-5 μg/mL against all strains tested. Hyphal formation in RPMI-1640, Spider and GlcNAc medium, adhesion to abiotic polystyrene surfaces and surfaces of A549 cells, could be inhibited by IBC. Most important, IBC could inhibit the C. albicans biofilm formation and development. PI staining tests showed that IBC could increase the cell membrane permeability, suggesting the damages to the fungal cell membrane. IBC was further demonstrated to induce excessive ROS production in C. albicans planktonic cells and its mature biofilms, as revealed by DCFH fluorescence detection through flowcytometry and relative fluorescence intensity analysis (with a microplate reader). The roles of ROS in the antifungal activity of IBC were further confirmed through antioxidant rescue assays in MIC and biofilm formation tests. Compared to its antifungal activity, the cytotoxicity against mammalian cells was low, indicating its potential in developing antifungal therapies.

Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis-benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 μg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH-DA staining suggested its anti-Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N-acetyl-cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti-Candida therapies.

BACKGROUND AND AIM:In this study, a deep learning algorithm was used to predict the survival rate of colon cancer (CC) patients, and compared its performance with traditional Cox regression. METHODS:In this population-based cohort study, we used the characteristics of patients diagnosed with CC between 2010 and 2015 from the Surveillance, Epidemiology and End Results (SEER) database. The population was randomized into a training set (n = 10 596, 70%) and a test set (n = 4536, 30%). Brier scores, area under the (AUC) receiver operating characteristic curve and calibration curves were used to compare the performance of the three most popular deep learning models, namely, artificial neural networks (ANN), deep neural networks (DNN), and long-short term memory (LSTM) neural networks with Cox proportional hazard (CPH) model. RESULTS:In the independent test set, the Brier values of ANN, DNN, LSTM and CPH were 0.155, 0.149, 0.148, and 0.170, respectively. The AUC values were 0.906 (95% confidence interval [CI] 0.897-0.916), 0.908 (95% CI 0.899-0.918), 0.910 (95% CI 0.901-0.919), and 0.793 (95% CI 0.769-0.816), respectively. Deep learning showed superior promising results than CPH in predicting CC specific survival. CONCLUSIONS:Deep learning showed potential advantages over traditional CPH models in terms of prognostic assessment and treatment recommendations. LSTM exhibited optimal predictive accuracy and has the ability to provide reliable information on individual survival and treatment recommendations for CC patients.

Natural products have always been a treasure trove for clinical drug development and a source of inspiration for lead compounds in the process of new drug discovery. However, two-dimensional cell cultures and animal models in the traditional drug development model have serious limitations in generalizing human physiopathology and cannot accurately predict the real clinical response of the human body to drugs, which brings obstacles and challenges to drug evaluation. Organ-on-a-chip (OoC) is an emerging technology based on microfluidic platforms and in vitro cell culture that can mimic the physiological environment and function of human organs for disease modeling and drug evaluation. In this review, we explore several major examples of how human single-OoC systems can be used to simulate complex disease models and outline recent advances in organoids for natural drug screening. Finally, we summarize the challenges and future trends that OoCs must overcome in drug discovery and development. Overall, this review highlights that OoCs, instead of animal models, open new avenues for natural drug development and evaluation, therapeutic innovation, and in vivo embodiment of personalized medicine.