A review of deep learning approaches for multimodal image segmentation of liver cancer.

This review examines the recent developments in deep learning (DL) techniques applied to multimodal fusion image segmentation for liver cancer. Hepatocellular carcinoma is a highly dangerous malignant tumor that requires accurate image segmentation for effective treatment and disease monitoring. Multimodal image fusion has the potential to offer more comprehensive information and more precise segmentation, and DL techniques have achieved remarkable progress in this domain. This paper starts with an introduction to liver cancer, then explains the preprocessing and fusion methods for multimodal images, then explores the application of DL methods in this area. Various DL architectures such as convolutional neural networks (CNN) and U-Net are discussed and their benefits in multimodal image fusion segmentation. Furthermore, various evaluation metrics and datasets currently used to measure the performance of segmentation models are reviewed. While reviewing the progress, the challenges of current research, such as data imbalance, model generalization, and model interpretability, are emphasized and future research directions are suggested. The application of DL in multimodal image segmentation for liver cancer is transforming the field of medical imaging and is expected to further enhance the accuracy and efficiency of clinical decision making. This review provides useful insights and guidance for medical practitioners.

Paxbp1 Is Indispensable for the Maintenance of Epidermal Homeostasis.

The mammalian epidermis is a structurally complex tissue that serves critical barrier functions, safeguarding the organism from the external milieu. The development of the epidermis is governed by sophisticated regulatory processes. However, the precise mechanism maintaining epidermal homeostasis remains incompletely elucidated. Recent studies have identified Paxbp1, an evolutionarily conserved protein, as being involved in the developmental regulation of various cells, tissues, and organs. Nonetheless, its role in skin development has not been explored. In this study, we report that the targeted deletion of Paxbp1 in epidermal keratinocytes mediated by keratin 14-Cre leads to severe disruption in skin architecture. Mice deficient in Paxbp1 exhibited a substantially reduced epidermal thickness and pronounced separation at the dermal-epidermal junction upon birth. Mechanistically, we demonstrate that the absence of Paxbp1 hinders cellular proliferation, marked by a halt in cell cycle transition, suppressed gene expression of proliferation, and a compromised DNA replication pathway in basal keratinocytes, resulting in the thinning of the skin epidermis. Moreover, molecules and pathways associated with hemidesmosome assembly were impaired in Paxbp1-deficient keratinocytes, culminating in the detachment of the skin epidermal layer. Therefore, our study highlights an indispensable role of Paxbp1 in the maintenance of epidermal homeostasis.

HPV-YAP1 oncogenic alliance drives malignant transformation of fallopian tube epithelial cells.

High grade serous ovarian carcinoma (HGSOC) is the most common and aggressive ovarian malignancy. Accumulating evidence indicates that HGSOC may originate from human fallopian tube epithelial cells (FTECs), although the exact pathogen(s) and/or molecular mechanism underlying the malignant transformation of FTECs is unclear. Here we show that human papillomavirus (HPV), which could reach FTECs via retrograde menstruation or sperm-carrying, interacts with the yes-associated protein 1 (YAP1) to drive the malignant transformation of FTECs. HPV prevents FTECs from natural replicative and YAP1-induced senescence, thereby promoting YAP1-induced malignant transformation of FTECs. HPV also stimulates proliferation and drives metastasis of YAP1-transformed FTECs. YAP1, in turn, stimulates the expression of the putative HPV receptors and suppresses the innate immune system to facilitate HPV acquisition. These findings provide critical clues for developing new strategies to prevent and treat HGSOC.

Recipients' and Environmental Factors Affecting the Pregnancy Rates of a Large, Fresh In Vitro Fertilization-Embryo Transfer Program for Dairy Cows in a Commercial Herd in China.

The main objective of this study was to determine the influence of the recipient dairy cows' breed, lactation number, estrus condition, the type, location and volume of the corpus luteum (CL) and the time of year that the embryo transfer (ET) was performed on the pregnancy rates of a large, fresh in vitro fertilization-embryo transfer program for dairy cows in a commercial herd in China. The recipients were from a herd of dairy cows in Ningxia, a province in northwest China, and we statistically analyzed the data of 495 cows from 2021 to 2023. Cumulus oocyte complexes (COCS) were isolated from follicular fluid obtained through ovum pick-up (OPU) and oocytes were incubated 20-22 h for in vitro maturation (IVM). Embryos were obtained after 10-12 h of in vitro fertilization (IVF) and six days of in vitro culture (IVC). Embryos at the morula or blastocyst stage were transferred to randomly chosen recipients (n = 495). The influence of recipients' breed (Holstein or other), recipients' lactation number (heifers or cows), estrus type (natural or synchronized), CL type (homogeneous, CLhom or cavitary, CLcav), CL side (left or right), volume of the CL and season of transfer (spring, autumn or winter) on pregnancy rates were determined. The pregnancy rates were analyzed by binomial logistic regression with IBM SPSS statistics software, version 26. Pregnancy rates after ET to Holstein cows and other breeds were 43.49% and 42.68%, respectively (p > 0.05). Regarding age, pregnancy rates were 45.56% for heifers and 30.77% for cows (p < 0.05). Pregnancy rates following ET during natural and synchronized estrus were 44.41% and 41.5%, respectively (p > 0.05). Pregnancy rates with a left- or right-side CL were 40.18% and 45.65%, respectively (p > 0.05). The pregnancy rates achieved with a CLhom and CLcav were 44.44% and 39.68%, respectively (p < 0.05). The rates obtained in spring, autumn and winter were 49.26%, 46.02% and 34.64%, respectively (p < 0.05). Moreover, it was found that pregnancy rates were higher in recipients with a CL volume measuring greater than 10 cm3 compared with those with a CL volume measuring less than 10 cm3 (p < 0.05). The comparisons showed that recipients' breed, estrus type or side of the CL had no effect, but the recipients' lactation number, ET season and the type and volume of the CL have significant effects on pregnancy rates during ET.

[Early gait analysis after total knee arthroplasty based on artificial intelligence dynamic image recognition].

OBJECTIVE: To explore early postoperative gait characteristics and clinical outcomes after total knee arthroplasty (TKA). METHODS: From February 2023 to July 2023, 26 patients with unilateral knee osteoarthritis (KOA) were treated with TKA, including 4 males and 22 females, aged from 57 to 85 years old with an average of (67.58±6.49) years old;body mass index (BMI) ranged from 18.83 to 38.28 kg·m-2 with an average of (26.43±4.15) kg·m-2;14 patients on the left side, 12 patients on the right side;according to Kellgren-Lawrence(K-L) classification, 6 patients with grade Ⅲ and 20 patients with grade IV;the courses of disease ranged from 1 to 14 years with an average of (5.54±3.29) years. Images and videos of standing up and walking, walking side shot, squatting and supine kneeling were taken with smart phones before operation and 6 weeks after operation. The human posture estimation framework OpenPose were used to analyze stride frequency, step length, step length, step speed, active knee knee bending angle, stride length, double support phase time, as well as maximum hip flexion angle and maximum knee bending angle on squatting position. Western Ontario and McMaster Universities (WOMAC) arthritis index and Knee Society Score (KSS) were used to evaluate clinical efficacy of knee joint. RESULTS: All patients were followed up for 5 to 7 weeks with an average of (6.00±0.57) weeks. The total score of WOMAC decreased from (64.85±11.54) before operation to (45.81±7.91) at 6 weeks after operation (P<0.001). The total KSS was increased from (101.19±9.58) before operation to (125.50±10.32) at 6 weeks after operation (P<0.001). The gait speed, stride frequency and stride length of the affected side before operation were (0.32±0.10) m·s-1, (96.35±24.18) steps·min-1, (0.72±0.14) m, respectively;and increased to (0.48±0.11) m·s-1, (104.20±22.53) steps·min-1, (0.79±0.10) m at 6 weeks after operation (P<0.05). The lower limb support time and active knee bending angle decreased from (0.31±0.38) s and (125.21±11.64) ° before operation to (0.11±0.04) s and (120.01±13.35) ° at 6 weeks after operation (P<0.05). Eleven patients could able to complete squat before operation, 13 patients could able to complete at 6 weeks after operation, and 9 patients could able to complete both before operation and 6 weeks after operation. In 9 patients, the maximum bending angle of crouching position was increased from 76.29° to 124.11° before operation to 91.35° to 134.12° at 6 weeks after operation, and the maximum bending angle of hip was increased from 103.70° to 147.25° before operation to 118.61° to 149.48° at 6 weeks after operation. CONCLUSION: Gait analysis technology based on artificial intelligence image recognition is a safe and effective method to quantitatively identify the changes of patients' gait. Knee pain of KOA was relieved and the function was improved, the supporting ability of the affected limb was improved after TKA, and the patient's stride frequency, stride length and stride speed were improved, and the overall movement rhythm of both lower limbs are more coordinated.

Photoredox-Catalyzed Phosphine-Mediated Successive Deoxygenation of Sulfonyl Oxime Salts Enables Anti-Markovnikov Hydrothiolation of Alkenes.

Stable and easy-to-handle sodium salts of sulfonyl oximes were first identified to proceed via visible-light-driven phophine-mediated successive deoxygenation to realize the anti-Markovnikov hydrothiolation of alkenes, which could serve as an odorless sulfur source. Mechanistic studies revealed that the key thiyl radical intermediate could be generated in situ from the sulfonyl oxime anion via a phosphine-mediated fragmentation and a sequential deoxygenation process. Notably, a wide range of alkenes, including acrylamides, acrylates, vinyl ketones, vinyl sulfones, and acrylonitriles, are competent substrates for this protocol, which is highly beneficial for the construction of structurally diversified organosulfur compounds.

Exosomes That Have Different Cellular Origins Followed by the Impact They Have on Prostate Tumor Development in the Tumor Microenvironment.

BACKGROUND: Prostate cancer (PCa) is the most common urinary tumor with the highest incidence rate and the second among the leading causes of death worldwide for adult males. In the worldwide cancer incidence rate, PCa is on the increase. The cancerous cells in the prostate and cells in the microenvironment surrounding the tumor communicate through signal transduction, which is crucial for the development and spread of PCa. RECENT FINDINGS: Exosomes are nanoscale vesicles released into body fluids by various cells that can aid intercellular communication by releasing nucleic acids and proteins. Exosomes published by different types of cells in the tumor microenvironment can have varying impacts on the proliferation and growth of tumor cells via various signaling pathways, modes of action, and secreted cytokines. CONCLUSION: The main purpose of this review is to describe the effects of different cell-derived exosomes in the tumor microenvironment of PCa on the progression of tumor cells, as well as to summarize and discuss the prospects for the application of exosomes in the treatment and diagnosis of PCa.

Multi-dimensional signals coupling of simultaneous acquisition stripping current with laser-induced breakdown spectroscopy for accurate analysis of Cd(II) in coexisting Cu(II).

BACKGROUND: Despite significant advancements in detecting Cd(II) using nanomaterials-modified sensitive interfaces, most detection methods rely solely on a single electrochemical stripping current to indicate concentration. This approach often overlooks potential inaccuracies caused by interference from coexisting ions. Therefore, establishing multi-dimensional signals that accurately reflect Cd(II) concentration in solution is crucial. RESULTS: In this study, we developed a system integrating concentration, electrochemical stripping current, and laser-induced breakdown spectroscopy (LIBS) characteristic peak intensity through in-situ laser-induced breakdown spectroscopy and electrochemical integrated devices. By simultaneously acquiring multi-dimensional signals to dynamically track the electrochemical deposition and stripping processes, we observed that replacement reactions occur between Cu(II) and Cd(II) on the surface of Ru-doped MoS2 modified carbon paper electrodes (Ru-MoS2/CP). These reactions facilitate the oxidation of Cd(0) to Cd(II) during the stripping process, significantly increasing the currents of Cd(II). Remarkably, the ingenious design of the Ru-MoS2 sensitive interface allowed for the undisturbed deposition of Cu(II) and Cd(II) during the electrochemical deposition process. Consequently, our in-situ integrated device achieved accurate detection of Cd(II) in complex environments, boasting a detection sensitivity of 8606.5 counts µM⁻1. SIGNIFICANCE: By coupling multi-dimensional signals from stripping current and LIBS spectra, we revealed the interference process between Cu(II) and Cd(II), providing valuable insights for accurate electrochemical analysis of heavy metal ions in complex water environments.

High-Entropy-Inspired Multicomponent Electrical Double Layer Structure Design for Stable Zinc Metal Anodes.

Regulating the electrical double layer (EDL) structure can enhance the cycling stability of Zn metal anodes, however, the effectiveness of this strategy is significantly limited by individual additives. Inspired by the high-entropy (HE) concept, we developed a multicomponent (MC) EDL structure composed of La3+, Cl-, and BBI anions by adding dibenzenesulfonimide (BBI) and LaCl3 additives into ZnSO4 electrolytes (BBI/LaCl3/ZnSO4). Specifically, La3+ ions accumulate within EDL to shield the net charges on the Zn surface, allowing more BBI anions and Cl- ions to enter this region. Consequently, this unique MC EDL enables Zn anodes to simultaneously achieve uniform electric field, robust SEI layer, and balanced reaction kinetics. Moreover, the synergistic parameter - a novel descriptor for quantifying collaborative improvement - was first proposed to demonstrates the synergistic effect between BBI and LaCl3 additives. Benefitting from these advantages, Zn metal anodes achieved a high reversibility of 99.5 % at a depth of discharge (DoD) of 51.3 %, and Zn|MnO2 pouch cells exhibited a stable cycle life of 100 cycles at a low N/P ratio of 2.9.

Effectiveness of utilizing step-monitoring devices to prevent and treat obesity in children and adolescents: A systematic review and meta-analysis.

Background: Children and adolescents who are overweight and obese represent a growing public health issue. The use of step-monitoring devices as an intervention tool may be a simple, cost-effective, and easily replicable solution for addressing obesity in children and adolescents. No prior systematic reviews have evaluated the effectiveness of utilizing step-monitoring devices as an intervention method for obesity in children and adolescents. Methods: Previous studies on using step-monitoring devices to prevent and treat obesity in children and adolescents were identified in the following databases: Web of Science, EMBASE, PubMed, Cochrane Library, SPORTDiscus, and SCOPUS. The search period for each database ranged from the year of their inception to 8 March 2023 (updated in June 2024). Meta-analyses were performed for mean differences (MDs) in body mass index (BMI), BMI z-score (BMI-Z), body fat, waist circumference, and body weight. Results: From 12,907 relevant records, 23 studies were included in this meta-analysis. The included studies were mainly at low risk of bias, except for blinding. Step-monitoring device-based interventions had significant effects in reducing BMI-Z (MD -0.06; 95% CI -0.10 to -0.02), body fat (MD -0.95%; 95% CI -1.35 to -0.54), and body weight (MD -1.23 kg; 95% CI -2.36 to -0.10). However, there was no significant effect on BMI (MD -0.16 kg/m2; 95% CI -0.55 to 0.22) and waist circumference (MD -0.33 cm; 95% CI -1.23 to 0.58). Subgroup analyses indicated that participants who were overweight or obese showed greater intervention effects on BMI and BMI-Z compared to participants with normal weight. The programs with an intervention duration of ≤6 months presented a greater intervention effect on BMI-Z than those with an intervention duration of more than 6 months. The programs that established goals had a greater intervention effect on body fat than those that did not. Conclusions: Step-monitoring devices may be an effective and generalizable intervention tool for the prevention and treatment of obesity in children and adolescents. Future studies should further explore how to set step goals and the duration of interventions to achieve better intervention effects.

Comparison of three different internal fixation methods in the treatment of femoral neck fracture.

Objective: This study aimed to assess the efficacy of three different fixation methods in treating femoral neck fractures in young patients. Methods: A retrospective analysis was conducted on 35 young patients with femoral neck fractures who underwent surgical treatment. Among them, 16, 12, and 7 patients underwent fixation with three cannulated compression screws (3CS), the femoral neck system (FNS), and the compound compression system (CCS), respectively. Data, including fracture classification, injury-to-surgery time, surgery duration, intraoperative blood loss, fluoroscopy instances, fracture healing time, complications, and Harris score at the final follow-up, were collected and analyzed to compare clinical outcomes among the three fixation methods. Results: All patients were followed for at least 6 months, exhibiting no significant differences in age, gender, injury side, fracture type, or injury-to-operation time among the three groups (P > 0.05). The FNS and CCS groups exhibited shorter operation durations and fewer intraoperative fluoroscopy instances compared to the 3CS group (P < 0.01). Despite the minimally invasive nature of 3CS, the FNS and CCS groups experienced higher intraoperative blood loss (P < 0.01). During follow-up, only one patient with 3CS fixation developed nonunion. Additionally, patients treated with 3CS demonstrated a higher incidence of femoral head necrosis and severe femoral neck shortening than the FNS and CCS groups. Excluding patients with combined nonunion, no significant difference in mean fracture healing time was observed among the three groups (P > 0.05). At the last follow-up, the FNS and CCS groups showed higher Harris scores (P < 0.05). Conclusions: Both FNS and CCS are effective internal fixation systems for the treatment of femoral neck fractures in young patients, yielding more satisfactory clinical functional outcomes than 3CS. Comparatively, the CCS system presents a higher risk of iatrogenic rotation of the proximal fracture segment. Therefore, we advocate the insertion of two to three 2.5 mm Kirschner wires from the upper edge of the femoral neck along the axial direction before CCS lag screw insertion to resist iatrogenic rotational stress.

Flexible/Regenerative Nanosensor with Automatic Sweat Collection for Cytokine Storm Biomarker Detection.

The real-time monitoring of low-concentration cytokines such as TNF-α in sweat can aid clinical physicians in assessing the severity of inflammation. The challenges associated with the collection and the presence of impurities can significantly impede the detection of proteins in sweat. This issue is addressed by incorporating a nanosphere array designed for automatic sweat transportation, coupled with a reusable sensor that employs a Nafion/aptamer-modified MoS2 field-effect transistor. The nanosphere array with stepwise wettability enables automatic collection of sweat and blocks impurities from contaminating the detection zone. This device enables direct detection of TNF-α proteins in undiluted sweat, within a detection range of 10 fM to 1 nM. The use of an ultrathin, ultraflexible substrate ensures stable electrical performance, even after up to 30 extreme deformations. The findings indicate that in clinical scenarios, this device could potentially provide real-time evaluation and management of patients' immune status via sweat testing.

Synergistic effect between S and Te enhancing the electrochemical behavior of heteroatomic TeS-x cathodes in aqueous Zn-TeS batteries.

Aqueous Zn-S batteries (AZSBs) have garnered increasing attention in the energy storage field owing to their high capacity, energy density, and cost effectiveness. Nevertheless, sulfur (S) cathodes face challenges, primarily stemming from sluggish reaction kinetics and the formation of an irreversible byproduct (SO42-) during the charge, hindering the progress of AZSBs. Herein, Te-S bonds within S-based cathodes were introduced to enhance electron and ion transport and facilitate the conversion reaction from zinc sulfide (ZnS) to S. This was achieved by constructing heteroatomic TeS-x@Ketjen black composite cathodes (HM-TeS-x@KB, where x  = 36, 9, and 4). The HM-TeS-9@KB electrode exhibits long-term cycling stability, maintaining a capacity decay rate of 0.1 % per cycle over 450 cycles at a current density of 10 A g-1. Crucially, through a combination of experimental data analysis and theoretical calculations, the impact mechanism of Te on the charge and discharge of S active materials within the HM-TeS-9@KB cathode in AZSBs was investigated. The presence of Te-S bonds boost the intrinsic conductivity and wettability of the HM-TeS-9@KB cathode. Furthermore, during the charge, the interaction of preferentially oxidized Te with S atoms within ZnS promotes the oxidation reaction from ZnS to S and suppresses the irreversible side reaction between ZnS and H2O. These findings indicate that the heteroatomization of chalcogen S molecules represents a promising approach for enhancing the electrochemical performance of S cathodes in AZSBs.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

A ghost moth olfactory prototype of the lepidopteran sex communication.

Sex role differentiation is a widespread phenomenon. Sex pheromones are often associated with sex roles and convey sex-specific information. In Lepidoptera, females release sex pheromones to attract males, which evolve sophisticated olfactory structures to relay pheromone signals. However, in some primitive moths, sex role differentiation becomes diverged. Here, we introduce the chromosome-level genome assembly from ancestral Himalaya ghost moths, revealing a unique olfactory evolution pattern and sex role parity among Lepidoptera. These olfactory structures of the ghost moths are characterized by a dense population of trichoid sensilla, both larger male and female antennal entry parts of brains, compared to the evolutionary later Lepidoptera. Furthermore, a unique tandem of 34 odorant receptor 19 homologs in Thitarodes xiaojinensis (TxiaOr19) has been identified, which presents overlapped motifs with pheromone receptors (PRs). Interestingly, the expanded TxiaOr19 was predicted to have unconventional tuning patterns compared to canonical PRs, with nonsexual dimorphic olfactory neuropils discovered, which contributes to the observed equal sex roles in Thitarodes adults. Additionally, transposable element activity bursts have provided traceable loci landscapes where parallel diversifications occurred between TxiaOr19 and PRs, indicating that the Or19 homolog expansions were diversified to PRs during evolution and thus established the classic sex roles in higher moths. This study elucidates an olfactory prototype of intermediate sex communication from Himalaya ghost moths.

Enhanced photocatalytic removal of bromate in drinking water by Au/TiO2 under ultraviolet light.

The photo-reduction of bromate (BrO3 -) has attracted much attention due to the carcinogenesis and genotoxicity of BrO3 - in drinking water. In this study, a heterojunction photocatalyst was developed by depositing Au nanoparticles (NPs) onto P25 TiO2 NPs through a one-pot, solvent-thermal process. Due to the unique properties of Au, the Au NPs deposited on the TiO2 surface created a Schottky barrier between the metal and the semiconductor, leading to an effective separation of photo-generated charge carriers as the Au nanoparticles served as electron sinks. The Au/TiO2 photocatalyst demonstrated efficient reduction of BrO3 - under UV light illumination without the need for sacrificial agents. The effect of different Au loading of Au/TiO2 was systematically investigated for its influence on the generation of electrons and the reduction ability of BrO3 -. The results indicate that the 1% Au/TiO2 catalyst exhibited a higher concentration of localized electrons, rendering it more effective in BrO3 - removal. The photocatalytic efficiency for BrO3 - reduction decreased upon the addition of K2S2O8 as an electron quencher, suggesting that the primary factor in this photo-reduction process was the availability of electrons. These findings hold promise for the potential application of the Au/TiO2 catalyst in the removal of BrO3 - from drinking water through photo-reduction.

Metabolomic landscape of renal cell carcinoma in von Hippel-Lindau syndrome in a Chinese cohort.

Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant disorder, where renal cell carcinoma (RCC) serves as a significant cause of mortality. We collected peripheral blood from 61 VHL-RCC patients and 31 healthy individuals, along with 19 paired RCC tumor and adjacent non-malignant samples. Using liquid chromatography-mass spectrometry, we identified 238 plasma and 241 tissue differentially abundant metabolites (DAMs), highlighting key pathways such as arginine and proline metabolism. The top 10 of the 23 DAMs, common to both plasma and tissue, were instrumental in constructing a high-performance diagnostic model. These DAMs demonstrated significant correlations with VHL gene mutation types. Cox regression analysis revealed that plasma levels of N2,N2-dimethylguanosine were associated with the timing of RCC onset in VHL patients, acting as an independent predictive factor. This study enhances diagnostic accuracy for this rare condition and opens new avenues for exploring metabolic mechanisms of the disease and potential therapeutic directions.

[Phenotypic drug discovery promotes research and development of innovative drugs based on traditional Chinese medicine].

Traditional Chinese medicine with rich resources in China and definite therapeutic effects on complex diseases demonstrates great development potential. However, the complex composition, the unclear pharmacodynamic substances and mechanisms of action, and the lack of reasonable methods for evaluating clinical safety and efficacy have limited the research and development of innovative drugs based on traditional Chinese medicine. The progress in cutting-edge disciplines such as artificial intelligence and biomimetics, especially the emergence of cell painting and organ-on-a-chip, helps to identify and characterize the active ingredients in traditional Chinese medicine based on the changes in model characteristics, thus providing more accurate guidance for the development and application of traditional Chinese medicine. The application of phenotypic drug discovery in the research and development of innovative drugs based on traditional Chinese medicine is gaining increasing attention. In recent years, the technology for phenotypic drug discovery keeps advancing, which improves the early discovery rate of new drugs and the success rate of drug research and development. Accordingly, phenotypic drug discovery gradually becomes a key tool for the research on new drugs. This paper discusses the enormous potential of traditional Chinese medicine in the discovery and development of innovative drugs and illustrates how the application of phenotypic drug discovery, supported by cutting-edge technologies such as cell painting, deep learning, and organ-on-a-chip, propels traditional Chinese medicine into a new stage of development.