A Call for Innovative Translational and Clinical Research to Address China's Unique Cancer Landscape.

The Chinese government has, in recent decades, implemented various administrative laws and regulatory policies to expedite cancer therapeutic development, boosting research and development pipelines for domestic pharmaceutical companies and clinical trials; however, China faces unique challenges given the high prevalence of certain cancer types and distinct disease burdens, some of which are frequently overlooked by international pharmaceutical companies. Given the substantial unmet need for China-specific cancer care, it is crucial to promote the development of innovative pharmaceutical and clinical research in China, with a particular emphasis on addressing tumors most prevalent in its population.

Dipole Moment Modulation of Terminal Groups Enables Asymmetric Acceptors Featuring Medium Bandgap for Efficient and Stable Ternary Organic Solar Cells.

This study puts forth a novel terminal group design to develop medium-bandgap Y-series acceptors beyond conventional side-chain engineering. We focused on the strategical integration of an electron-donating methoxy group and an electron-withdrawing halogen atom at benzene-fused terminal groups. This combination precisely modulated the dipole moment and electron density of terminal groups, effectively attenuating intramolecular charge transfer effect, and widening the bandgap of acceptors. The incorporation of these terminal groups yielded two asymmetric acceptors, named BTP-2FClO and BTP-2FBrO, both of which exhibited open-circuit voltage (VOC) as high as 0.96 V in binary devices, representing the highest VOCs among the asymmetric Y-series small molecule acceptors. More importantly, both BTP-2FClO and BTP-2FBrO exhibit modest aggregation behaviors and molecular crystallinity, making them suitable as a third component to mitigate excess aggregation of the PM6: BTP-eC9 blend and optimize the devices' morphology. As a result, the optimized BTP-2FClO-based ternary organic solar cells (OSCs) achieved a remarkable power conversion efficiency (PCE) of 19.34%, positioning it among the highest-performing OSCs. Our study highlights the molecular design importance on manipulating dipole moments and electron density in developing medium-bandgap acceptors, and offers a highly efficient third component for high-performance ternary OSCs.

Co-adsorbed self-assembled monolayer enables high-performance perovskite and organic solar cells.

Self-assembled monolayers (SAMs) have become pivotal in achieving high-performance perovskite solar cells (PSCs) and organic solar cells (OSCs) by significantly minimizing interfacial energy losses. In this study, we propose a co-adsorb (CA) strategy employing a novel small molecule, 2-chloro-5-(trifluoromethyl)isonicotinic acid (PyCA-3F), introducing at the buried interface between 2PACz and the perovskite/organic layers. This approach effectively diminishes 2PACz's aggregation, enhancing surface smoothness and increasing work function for the modified SAM layer, thereby providing a flattened buried interface with a favorable heterointerface for perovskite. The resultant improvements in crystallinity, minimized trap states, and augmented hole extraction and transfer capabilities have propelled power conversion efficiencies (PCEs) beyond 25% in PSCs with a p-i-n structure (certified at 24.68%). OSCs employing the CA strategy achieve remarkable PCEs of 19.51% based on PM1:PTQ10:m-BTP-PhC6 photoactive system. Notably, universal improvements have also been achieved for the other two popular OSC systems. After a 1000-hour maximal power point tracking, the encapsulated PSCs and OSCs retain approximately 90% and 80% of their initial PCEs, respectively. This work introduces a facile, rational, and effective method to enhance the performance of SAMs, realizing efficiency breakthroughs in both PSCs and OSCs with a favorable p-i-n device structure, along with improved operational stability.

Revisiting the CXCL13/CXCR5 axis in the tumor microenvironment in the era of single-cell omics: Implications for immunotherapy.

As one of the important members of the family of chemokines and their receptors, the CXCL13/CXCR5 axis is involved in follicle formation in normal lymphoid tissues and the establishment of somatic cavity immunity under physiological conditions, as well as being associated with a wide range of infectious, autoimmune, and tumoral diseases. Here in this review, we focus on its role in tumors. Traditional studies have found the axis to be both pro- and anti-tumorigenic, involving a variety of immune cells, including the tumor cells themselves and those in the tumor microenvironment (TME), and the prognostic significance of this axis is clinical context-dependent. With the development of techniques at the single-cell level, we were able to explain in detail the status of the CXCL13/CXCR5 axis in the TME based on real clinical samples and found that it involves a range of crucial intrinsic anti-tumor immune processes in the TME and is therefore important in tumor immunotherapy. We summarize the cellular subsets, physiological functions, and prognostic significance associated with this axis in the most promising immune checkpoint inhibitor (ICI) therapies of the day and summarize possible therapeutic ideas based on this axis. As with any TME study, the most important takeaway is that the complexity of the CXCL13/CXCR5 axis in TME suggests the importance of personalized therapy in tumor therapy.

Approaching 20% Efficiency in Ortho-Xylene Processed Organic Solar Cells by a Benzo[a]phenazine-Core-Based 3D Network Acceptor with Large Electronic Coupling and Long Exciton Diffusion Length.

High-performance organic solar cells often rely on halogen-containing solvents, which restrict the photovoltaic industry. Therefore, it is imperative to develop efficient organic photovoltaic materials compatible with halogen-free solvents. Herein, a series of benzo[a]phenazine (BP)-core-based small-molecule acceptors (SMAs) achieved through an isomerization chlorination strategy is presented, comprising unchlorinated NA1, 10-chlorine substituted NA2, 8-chlorine substituted NA3, and 7-chlorine substituted NA4. Theoretical simulations highlight NA3's superior orbit overlap length and tight molecular packing, attributed to interactions between the end group and BP unit. Furthermore, NA3 demonstrates dense 3D network structures and a record electronic coupling of 104.5 meV. These characteristics empower the ortho-xylene (o-XY) processed PM6:NA3 device with superior power conversion efficiency (PCE) of 18.94%, surpassing PM6:NA1 (15.34%), PM6:NA2 (7.18%), and PM6:NA4 (16.02%). Notably, the significantly lower PCE in the PM6:NA2 device is attributed to excessive self-aggregation characteristics of NA2 in o-XY. Importantly, the incorporation of D18-Cl into the PM6:NA3 binary blend enhances crystallographic ordering and increases the exciton diffusion length of the donor phase, resulting in a ternary device efficiency of 19.75% (certified as 19.39%). These findings underscore the significance of incorporating new electron-deficient units in the design of efficient SMAs tailored for environmentally benign solvent processing of OSCs.

Molecular Control of the Donor/Acceptor Interface Suppresses Charge Recombination Enabling High-Efficiency Single-Component Organic Solar Cells.

Single-component organic solar cells based on double cable polymers have achieved remarkable performance, with DCPY2 reaching a high efficiency of over 13%. In this study, DCPY2 is further optimized with an efficiency of 13.85%, maintaining a high fill factor (FF) without compromising the short circuit current. Despite its intermixed morphology, DCPY2 shows a reduced recombination rate compared to their binary counterpart (PBDB-T:Y-O6). This slower recombination in DCPY2 is attributed to the reduced wavefunction overlap of delocalized charges, achieved by spatially separating the donor and acceptor units with an alkyl linker, thereby restricting the recombination pathways. Adding 1,8-diiodooctane (DIO) into DCPY2 further reduced the recombination rate by facilitating acceptor aggregation, allowing free charges to become more delocalized. The DIO-assisted aggregation in DCPY2 (5% DIO) is evidenced by an increased pseudo-pure domain size of Y-O6. Fine molecular control at the donor/acceptor interface in the double-cable polymer achieves reduced non-geminate recombination under efficient charge generation, increased mobility, and charge carrier lifetime, thereby achieving superior performance. Nevertheless, the FF is still limited by relatively low mobility compared to the blend, suggesting the potential for further mobility improvement through enhanced higher-dimensional packing of the double-cable material.

Expression profiling and function analysis identified new genes regulating cumulus expansion and cumulus cell apoptosis in mouse oocytes.

In brief: Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos. Abstract: Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

High-Detectivity All-Polymer Photodiode Empowers Smart Vitality Surveillance and Computational Imaging Rivaling Silicon Diodes.

Near-infrared (NIR) organic photodetectors (OPDs), particularly all-polymer-based ones, hold substantial commercial promise in the healthcare and imaging sectors. However, the process of optimizing their active layer composition to achieve highly competitive figures of merit lacks a clear direction and methodology. In this work, celebrity polymer acceptor PY-IT into a more NIR absorbing host system PBDB-T:PZF-V, to significantly enhance the photodetection competence, is introduced. The refined all-polymer ternary broadband photodetector demonstrates superior performance metrics, including experimentally measured noise current as low as 6 fA Hz-1/2, specific detectivity reaching 8 × 1012 Jones, linear dynamic range (LDR) of 145 dB, and swift response speed surpassing 200 kHz, striking a fair balance between sensitivity and response speed. Comprehensive morphological and photophysical characterizations elucidate the mechanisms behind the observed performance enhancements in this study, which include reduced trap density, enhanced charge transport, diminished charge recombination, and balanced electron/hole mobilities. Moreover, the practical deployment potential of the proof-of-concept device in self-powered mode is demonstrated through their application in a machine learning-based cuffless blood pressure (BP) estimation system and in high-resolution computational imaging across complex environments, where they are found to quantitatively rival commercial silicon diodes.

Insulator Polymer Matrix Construction on All-Small-Molecule Photoactive Blend Towards Extrapolated 15000 Hour T80 Stable Devices.

To boost the stability of all-small-molecule (ASM) organic photovoltaic (OPV) blends, an insulator polymer called styrene-ethylene-butylene-styrene (SEBS) as morphology stabilizer is applied into the host system of small molecules BM-ClEH:BO-4Cl. Minor addition of SEBS (1 mg/ml in host solution) provides a significantly enhanced T80 value of 15000 hours (extrapolated), surpassing doping-free (0 mg/ml) and heavy doping (10 mg/ml) counterparts (900 hours, 30 hours). The material reproducibility and cost-effectiveness of the active layer will not be affected by this industrially available polymer, where the power conversion efficiency (PCE) can be well maintained at 15.02%, which is still a decent value for non-halogen solvent-treated ASM OPV. Morphological and photophysical characterizations clearly demonstrate SEBS's pivotal effect on suppressing the degradation of donor molecules and blend film's crystallization/aggregation reorganization, which protects the exciton dynamics effectively. This work pays meaningful attention to the ASM system stability, performs a smart strategy to suppress the film morphology degradation, and releases a comprehensive understanding of the mechanism of device performance reduction.

Immunoregulation of Glia after spinal cord injury: a bibliometric analysis.

Objective: Immunoregulation is a complex and critical process in the pathological process of spinal cord injury (SCI), which is regulated by various factors and plays an important role in the functional repair of SCI. This study aimed to explore the research hotspots and trends of glial cell immunoregulation after SCI from a bibliometric perspective. Methods: Data on publications related to glial cell immunoregulation after SCI, published from 2004 to 2023, were obtained from the Web of Science Core Collection. Countries, institutions, authors, journals, and keywords in the topic were quantitatively analyzed using the R package "bibliometrix", VOSviewer, Citespace, and the Bibliometrics Online Analysis Platform. Results: A total of 613 papers were included, with an average annual growth rate of 9.39%. The papers came from 36 countries, with the United States having the highest output, initiating collaborations with 27 countries. Nantong University was the most influential institution. We identified 3,177 authors, of whom Schwartz, m, of the Weizmann Institute of Science, was ranked first regarding both field-specific H-index (18) and average number of citations per document (151.44). Glia ranked first among journals with 2,574 total citations. The keywords "microglia," "activation," "macrophages," "astrocytes," and "neuroinflammation" represented recent hot topics and are expected to remain a focus of future research. Conclusion: These findings strongly suggest that the immunomodulatory effects of microglia, astrocytes, and glial cell interactions may be critical in promoting nerve regeneration and repair after SCI. Research on the immunoregulation of glial cells after SCI is emerging, and there should be greater cooperation and communication between countries and institutions to promote the development of this field and benefit more SCI patients.

Role and action mechanisms of tPA in CRH-induced apoptosis of mouse oviductal epithelial and mural granulosa cells.

Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.

A Difluoro-Methoxylated Ending-Group Asymmetric Small Molecule Acceptor Lead Efficient Binary Organic Photovoltaic Blend.

Developing a new end group for synthesizing asymmetric small molecule acceptors (SMAs) is crucial for achieving high-performance organic photovoltaics (OPVs). Herein, an asymmetric small molecule acceptor, BTP-BO-4FO, featuring a new difluoro-methoxylated end-group is reported. Compared to its symmetric counterpart L8-BO, BTP-BO-4FO exhibits an upshifted energy level, larger dipole moment, and more sequential crystallinity. By adopting two representative and widely available solvent additives (1-chloronaphthalene (CN) and 1,8-diiodooctane (DIO)), the device based on PM6:BTP-BO-4FO (CN) photovoltaic blend demonstrates a power conversion efficiency (PCE) of 18.62% with an excellent open-circuit voltage (VOC) of 0.933 V, which surpasses the optimal result of L8-BO. The PCE of 18.62% realizes the best efficiencies for binary OPVs based on SMAs with asymmetric end groups. A series of investigations reveal that optimized PM6:BTP-BO-4FO film demonstrates similar molecular packing motif and fibrillar phase distribution as PM6:L8-BO (DIO) does, resulting in comparable recombination dynamics, thus, similar fill factor. Besides, it is found PM6:BTP-BO-4FO possesses more efficient charge generation, which yields better VOC-JSC balance. This study provides a new ending group that enables a cutting-edge efficiency in asymmetric SMA-based OPVs, enriching the material library and shed light on further design ideas.

Precisely Controlling Polymer Acceptors with Weak Intramolecular Charge Transfer Effect and Superior Coplanarity for Efficient Indoor All-Polymer Solar Cells with over 27% Efficiency.

Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application.

Electroacupuncture and carbamazepine for patients with trigeminal neuralgia: a randomized, controlled, 2 × 2 factorial trial.

BACKGROUND: Trigeminal neuralgia (TN) is difficult to treat due to its severe pain intensity and recurring episodes, which significantly impact quality of life. OBJECTIVES: We aimed to assess the effectiveness of electroacupuncture (EA) in alleviating the pain intensity in TN, and to determine whether EA combined with low-dosage carbamazepine (CBZ) has a synergistic effect. METHODS: A multi-centre, randomized, 2 × 2 factorial trial was conducted. Participants who met the inclusion criteria received active EA or sham EA for 60 min, three times a week for four weeks; CBZ (300 mg per day) or placebo for four weeks. The primary outcome was the change in visual analog scale (VAS) score from baseline to weeks 2, 4, 16, and 28. Secondary outcomes included quality of life and adverse events. RESULTS: A total of 120 participants (75 females and 45 males; mean (SD) age, 58.5 (15.3) years) were included. The main effects of EA and CBZ were significant (P < 0.001), and there was a significant interaction was identified between the interventions (P = 0.041). Participants who received EA (mean difference [MD], -0.3 [95% CI, -0.40 to -0.20] at week 2; -1.6 [-1.70 to -1.50] at week 4; -1.1 [-1.31 to -0.89] at week 16; -0.8 [-1.01 to -0.59] at week 28), CBZ (MD, -0.6 [95% CI, -0.70 to -0.50] at week 2; -0.9 [-1.03 to -0.77] at week 4, -0.2 [-0.41 to 0.01] at week 16, 0.2 [-0.01 to 0.41] at week 28), and the combination of both (MD, -1.8 [95% CI, -1.90 to -1.70] at week 2; -3.7 [-3.83 to -3.57] at week 4, -3.4 [-3.61 to -3.19] at week 16, -2.9 [-3.11 to -2.69] at week 28) had a greater reduction in VAS score over the treatment phase than their respective control groups (sham EA, placebo, and sham EA plus placebo). EA-related adverse events (6/59, 10.17%) were lower than that of CBZ (15/59, 25.42%) during the whole phases. CONCLUSIONS: EA or CBZ alone are effective treatments for TN, while the combination of EA and low-dosage CBZ exerts a greater benefit. These findings in this trial demonstrate that the combination of EA and low-dosage CBZ may be clinically effective under certain circumstances. TRIAL REGISTRATION: NCT03580317.

Use of Phase-Angle Model for Full-Field 3D Reconstruction under Efficient Local Calibration.

Currently, 3D reconstruction methods in structured light are generally implemented in a pre-calibrated area. To realize a full-field reconstruction, the calibration plate can be moved to multiple positions in a time-consuming manner, or the whole field can be calibrated with the help of a large calibration plate, which is more costly. In this paper, we address this problem by proposing a method for obtaining a global phase-angle model under a locally calibrated region, and based on this relationship, we investigate and analyze the reconstruction inside and outside of the calibrated zone. The results show that the method can reconstruct the object outside of the calibration zone completely, and can keep the planarity error around 0.1 mm and the sphericity error below 0.06 mm. The method only requires local calibration of the projected fringes at the two calibration positions to realize the 3D reconstruction of the full-field, which makes the method more advantageous.

Role and action mechanisms of miR-149 and miR-31 in regulating function of pig cumulus cells and oocytes.

Understanding the mechanisms for oocyte maturation and optimizing the protocols for in vitro maturation (IVM) are greatly important for improving developmental potential of IVM oocytes. The miRNAs expressed in cumulus cells (CCs) play important roles in oocyte maturation and may be used as markers for selection of competent oocytes/embryos. Although a recent study from our group identified several new CCs-expressed miRNAs that regulate cumulus expansion (CE) and CC apoptosis (CCA) in mouse oocytes, validation of these findings and further investigation of mechanisms of action in other model species was essential before wider applications. By using both in vitro and in vivo pig oocyte models with significant differences in CE, CCA and developmental potential, the present study validated that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes. We demonstrated that miR-149 and miR-31 targeted SMAD family member 6 (SMAD6) and transforming growth factor ß2 (TGFB2), respectively, in the transforming growth factor-ß (TGF-ß) signaling. Furthermore, both miR-149 and miR-31 increased CE and decreased CCA via activating SMAD family member 2 (SMAD2) and increasing the expression of SMAD2 and SMAD family member 4. In conclusion, the present results show that miR-149 and miR-31 improved CE and developmental potential while suppressing CCA of pig oocytes by activating the TGF-ß signaling, suggesting that they might be used as markers for pig oocyte quality.

Efficient all-small-molecule organic solar cells processed with non-halogen solvent.

All-small-molecule organic solar cells with good batch-to-batch reproducibility combined with non-halogen solvent processing show great potential for commercialization. However, non-halogen solvent processing of all-small-molecule organic solar cells are rarely reported and its power conversion efficiencies are very difficult to improve. Herein, we designed and synthesized a small molecule donor BM-ClEH that can take advantage of strong aggregation property induced by intramolecular chlorine-sulfur non-covalent interaction to improve molecular pre-aggregation in tetrahydrofuran and corresponding micromorphology after film formation. Tetrahydrofuran-fabricated all-small-molecule organic solar cells based on BM-ClEH:BO-4Cl achieved high power conversion efficiencies of 15.0% in binary device and 16.1% in ternary device under thermal annealing treatment. In contrast, weakly aggregated BM-HEH without chlorine-sulfur non-covalent bond is almost inefficient under same processing conditions due to poor pre-aggregation induced disordered π-π stacking, indistinct phase separation and exciton dissociation. This work promotes the development of non-halogen solvent processing of all-small-molecule organic solar cells and provides further guidance.

Over 19 % Efficiency Organic Solar Cells Enabled by Manipulating the Intermolecular Interactions through Side Chain Fluorine Functionalization.

Fluorine side chain functionalization of non-fullerene acceptors (NFAs) represents an effective strategy for enhancing the performance of organic solar cells (OSCs). However, a knowledge gap persists regarding the relationship between structural changes induced by fluorine functionalization and the resultant impact on device performance. In this work, varying amounts of fluorine atoms were introduced into the outer side chains of Y-series NFAs to construct two acceptors named BTP-F0 and BTP-F5. Theoretical and experimental investigations reveal that side-chain fluorination significantly increase the overall average electrostatic potential (ESP) and charge balance factor, thereby effectively improving the ESP-induced intermolecular electrostatic interaction, and thus precisely tuning the molecular packing and bulk-heterojunction morphology. Therefore, the BTP-F5-based OSC exhibited enhanced crystallinity, domain purity, reduced domain spacing, and optimized phase distribution in the vertical direction. This facilitates exciton diffusion, suppresses charge recombination, and improves charge extraction. Consequently, the promising power conversion efficiency (PCE) of 17.3 % and 19.2 % were achieved in BTP-F5-based binary and ternary devices, respectively, surpassing the PCE of 16.1 % for BTP-F0-based OSCs. This work establishes a structure-performance relationship and demonstrates that fluorine functionalization of the outer side chains of Y-series NFAs is a compelling strategy for achieving ideal phase separation for highly efficient OSCs.

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review).

Neddylation, akin to ubiquitination, represents a post­translational modification of proteins wherein neural precursor cell­expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8­mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti­CRC target.