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Background: Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression. Methods: A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools. Results: Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001]. Conclusion: Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.

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Over the last 30 years, despite considerable research and endeavors aimed at harnessing aptamers as pharmaceutical molecules, the progress in developing aptamer-based drugs has been falling short of expectations. Sequential steps of affinity molecule acquisition and functional screening are typically required for discovering affinity-based macromolecule therapeutics, which can be time-consuming and limiting in candidate selection. Additionally, aptamers often necessitate tedious postselection modifications to overcome pharmacokinetic limitations, which usually impede the binding affinity. Herein, we propose a novel in vitro screening platform termed Functional Aptamers in vitro Evolution (FAIVE), which integrates affinity molecule acquisition with functional screening and introduces chemical diversity during the process. This platform aims to rapidly generate functional aptamers capable of binding to target proteins and regulating their functions. Illustrated by targeting intranuclear RNA-protein interactions involving HIV-1 Tat protein and TAR RNA, FAIVE demonstrates a selection of functional aptamers with significant intracellular blocking effects. The study also explores lipid nanoparticle delivery systems to enhance intracellular delivery efficiency, expanding aptamer targeting potential to broader intracellular and intranuclear domains. This study emphasizes the potential of FAIVE to expedite the development of aptamer-based drugs and facilitate the creation of more versatile and effective therapeutics.

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The introduction of difluoromethylene moieties into organic molecules has garnered significant attention due to their profound influence on the physicochemical and biological properties of compounds. Nonetheless, the existing approaches for accessing difluoroalkanes from readily available feedstock chemicals remain limited. In this study, we present an efficient and modular protocol for the synthesis of difluorinated compounds from alkenes, employing the readily accessible reagent, ClCF2SO2Na, as a versatile "difluoromethylene" linchpin. By means of an organophotoredox-catalysed hydrochlorodifluoromethylation of alkenes, followed by a ligated boryl radical-facilitated halogen atom transfer (XAT) process, we have successfully obtained various difluorinated compounds, including gem-difluoroalkanes, gem-difluoroalkenes, difluoromethyl alkanes, and difluoromethyl alkenes, with satisfactory yields. The practical utility of this linchpin strategy has been demonstrated through the successful preparation of CF2-linked derivatives of complex drugs and natural products. This method opens up new avenues for the synthesis of structurally diverse difluorinated hydrocarbons and highlights the utility of ligated boryl radicals in organofluorine chemistry.

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Ochratoxin A (OTA) is a toxic metabolite commonly found in various foods and feedstuffs. Accurate and sensitive detection of OTA is needed for food safety and human health. Based on a common OTA-binding aptamer (OTABA), two structure-switching OTABAs, namely OTABA4 and OTABA3, were designed by configuring a split G-quadruplex and a split G-triplex, respectively, at the two ends of OTABA to construct aptasensors for the detection of OTA. The OTABA, G-quadruplex, and G-triplex all can capture the thioflavin T (ThT) probe, thereby enhancing the fluorescence intensity of ThT. Bonding with OTA could change the conformations of OTABA and G-quadruplex or G-triplex regions, resulting in the release of the captured ThT and diminution of its fluorescence intensity. Dual conformation changes in structure-switching OTABA synergistically amplified the fluorescence signal and improved the sensitivity of the aptasensor, especially for that with OTABA3. The detection limits of the OTABA4-ThT and OTABA3-ThT systems for OTA were 0.28 and 0.059 ng ml-1 , with a 1.4-fold and 6.7-fold higher sensitivity than that of the original OTABA-ThT system, respectively. They performed well in corn and peanut samples and met the requirements of the food safety inspections.

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Ochratoxin A (OTA), a typical mycotoxin contaminant found in various agricultural products and foods, poses a serious threat to human health. In this study, an aptasensor based on a novel fluorescence probe comprising a G-rich DNA sequence (G43) and thioflavin T (ThT) was designed via hybridization chain reaction (HCR) for the ultrasensitive detection of OTA. G43 is a concatemer of G-quadruplex and G-triplex (a G-quadruplex-like structure with one G-quartet removed), which can drastically enhance the fluorescence intensity of ThT. For this strategy to work, the OTA aptamer is pro-locked in a hairpin structure, denoted "hairpin-locked aptamer" (HL-Apt). OTA binds to HL-Apt, opens the hairpin structure, releases the trigger sequence, and initiates the HCR reaction to form a long DNA duplex and numerous side chains. The side chains combine entirely with the complementary DNA and liberate the pro-locked G43 DNA, dramatically enhancing the intensity of the ThT fluorescence signal. The fluorescence intensity correlates linearly with the OTA concentration between 0.02 and 2.00 ng mL-1, and the method has a detection limit of 0.008 ng mL-1. The developed aptasensor was used to detect OTA in foodstuffs with satisfactory results.

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Novel magnetic and fluorinated porous carbons (M-FPCs) with high fluorine content, large pore volume and specific surface area were first prepared by carbonizing and further fluorinating Fe-Zr bimetal-organic frameworks. The M-FPCs exhibit excellent adsorption performance toward perfluorinated compounds (PFCs), and the maximal adsorption capacity ranges from 518.1 to 919.3 mg g-1 for various PFCs. Based on this property, an environmental analytical method of dispersive solid-phase extraction (DSPE) using M-FPCs as adsorbents coupled with ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) was developed for the detection of trace PFCs. The linear range was as wide as 10-200 ng L-1, and low limit of detection (0.02-0.16 ng L-1) and good precision (relative standard deviation less than 6.11% for intra-day and inter-day) were achieved. This method was applied to the detection of trace PFCs in environmental water and soil samples with satisfactory results.

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Smilax glabra Roxb. (SGB) is a medicinal plant widely distributed in 17 countries worldwide. It is the primary raw material of the world-famous and best-selling functional food and beneficial tea. SGB was first recorded in Ben Cao Jing Ji Zhu of the Southern and Northern Dynasties (420-589 AD) and was reported for nutritional and medicinal properties for thousands of years. This review searched PubMed, Web of Science, and other databases for relevant literature on SGB species until April 2022. It aims to provide more integrated thinking, detailed awareness, and better knowledge of SGB. More than 200 chemical components have been discovered, including flavonoids, phenolic, phenolic acids, stilbenes, organic acids, phenylpropanoids, and others. Previous studies have demonstrated that SGB and its active ingredients show a wide range of pharmacological effects, including anti-infective, anti-cancer, anti-inflammatory, antioxidant, cardiovascular protection, etc. However, many studies on the biological activity of this plant were mainly based on crude extracts and active ingredients, and there is a lack of clinical studies and toxicity studies to support the development of drug design, development, and therapy. In summary, this review will provide specific and valuable suggestions and guidelines for further research and application of this plant in the medicinal field.

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The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation of unactivated alkenes with an inexpensive industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol is realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) with organophotoredox catalysis under blue light irradiation. A broad scope of readily accessible alkenes featuring a variety of functional groups and drug and natural product moieties could be selectively difluoromethylated with good efficiency in a metal-free manner. Combined experimental and computational studies suggest that the key XAT process of ClCF2H is both thermodynamically and kinetically favored over the hydrogen atom transfer pathway owing to the formation of a strong boron-chlorine (B-Cl) bond and the low-lying antibonding orbital of the carbon-chlorine (C-Cl) bond.

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Probing the adlayer structures on an electrode/electrolyte interface is one of the most important tasks in modern electrochemistry for clarifying the electrochemical processes. Herein, we have combined cyclic voltammetry and electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy techniques to explore the potential-dependent adlayer structures on Au(111) in a room-temperature ionic liquid of 1-butyl-3-methylimidazolium hexafluorophosphate (BMIPF6) without or with pyridine (Py). It is clearly found that the BMI+ cations strongly adsorb on the negatively charged surface with a flat-lying orientation, leaving a little space for Py adsorption. Upon increasing the potentials of the electrode, the variations of Raman band intensities and frequencies reveal that the interaction between the BMI+ cations and the Au surface becomes weak; meanwhile, the Py adsorption becomes strong, and its geometry turns from flat, tilted to vertical. Finally, BMI+ cations desorb and leave plenty of surface sites for Py adsorption in bulk solution, and a N-bonded compact Py adlayer is formed on the very positively charged surface. This causes obvious anodic peaks in cyclic voltammograms, and the peak currents increase with the square root of the scanning rate. The present work provides a fair molecular-level understanding of electrochemical interfaces and molecular adsorption of Py in ionic liquids.

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Large amounts of coexisting contamination in complex biofluid samples impede the quantified veracity of biomarkers, which is the key problem for disease confirmation. Herein, amyloid-like transformed bovine serum albumin inlaid with gold nanoparticles was used as a coating (BGC) on a substrate composed of silicon nanowires (SW; BGC-SW) under ambient conditions. After modification with the recognition group, BGC-SW could serve as an outstanding platform for the selective separation and sensitive detection of biomarkers in complicated biosamples. First, the BGC on SW with a large surface area exhibits excellent adhesion resistance. The attached amounts of contaminations in biofluids were decreased by over 78% compared with native bovine serum albumin (BSA) as the blocking agent. This is because the phase-transformed BSA coating provides stronger interactions with the SW than bare BSA, which results in a tighter attachment and more uniform coverage of the BGC. Furthermore, the gold matrix laid inside the antiadhesive coating ensures simple cross-linking with the recognition groups to selectively capture various biomarkers in complex biofluids and create a gentle release method. Circulating tumor cells (CTCs) were chosen as template biomarkers to verify the application of A-BGC-SW (BGC-SW modified with sgc8-aptamer) in various separation processes of untreated biofluids. The results showed that approximately six cells could be captured from a 1 mL fresh blood sample containing only 10 CTCs. The easy fabrication and excellent antiadhesion property endow A-BGC-SW with great potential in the field of biological separation.

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The HIV-Ι trans-activation responsive (TAR) RNA-trans-activator of transcription (Tat) protein complex is crucial for the efficient transcription of the integrated human immunodeficiency virus-I genome and is an established therapeutic target for AIDS diagnosis and treatment. Developing a sensitive strategy for the TAR RNA-binding ligand assay could provide antiviral leads with a radically new mechanism for the treatment of AIDS. Herein, a new TAR RNA-binding ligand assay platform was established using a signal amplification strategy that combines aggregation-induced emission (AIE) with a metal-enhanced fluorescence (MEF) concept. The tetraphenylethylene (TPE) derivative was labeled on the Tat peptide as a fluorescent molecule, while the TAR RNA was immobilized on the surface of the Fe3O4@Au@Ag@SiO2 nanoparticles (NPs) to specifically bind the TPE-Tat peptide. The TPE-Tat peptide was weakly emissive itself while emitting strongly in the NP-TAR-TPE-Tat complex by the AIE and MEF signal amplification effect. It was confirmed by known Tat peptide competitors that this system could be applied to the screening and detection of TAR RNA-binding ligands because they could replace the TPE-Tat peptide from the complex and make the system fluorescence decrease. When this system was adopted to test four candidate ligands, it was found that bisantrene had a favorable TAR RNA-binding ability. The proposed AIE-MEF strategy not only provides a sensitive and reliable method for the TAR RNA-binding ligand assay but also can avoid the influence of ligands on fluorescent detection in the conventional displacement assay.

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Covalent organic polymers (COPs) are promising adsorbents for the removal and detection of various types of pollutants. However, the preparation of COPs that exhibit uniform dispersion and good appearance at room temperature is challenging. Herein, fluorinated covalent organic polymers (F-COPs) with different morphologies were synthesized through the Schiff base reaction of 4,4-diamino-p-terphenyl (DT) and 2,3,5,6-tetrafluoroterephthalaldehyde (TFA). The as-prepared F-COPs could selectively adsorb perfluorinated compounds (PFCs) owing to their fluoro-affinity, hydrophobicity, hydrogen bonding, and electrostatic attraction. The adsorption kinetics and isotherm simulation results showed that the adsorption process conformed to the second-order kinetics and the Langmuir model. The saturated adsorption capacity calculated by the Langmuir model was found to be 323-667 mg/g. The F-COPs were applied to the treatment of simulated fluorine industrial wastewater, and the PFC removal efficiencies of 92.3-100.0% were achieved. Moreover, ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) was conducted for the detection of trace-level PFCs using F-COPs as dispersive solid-phase extraction (DSPE) adsorbents. The limits of detection were 0.05-0.13 ng/L and the limits of quantification were 0.17-0.43 ng/L. This study facilitates the synthesis of COPs at room temperature and extends the application of COPs as pretreated materials for environmental remediation and detection.

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In order to meet the requirements of pesticide residues' detection in complex matrix samples, the magnetic fluorinated multi-wall carbon nanotubes (M-F-MWCNTs) were prepared and applied as new QuEChERS clean-up materials. Combined with GC-MS, an improved QuEChERS method was successfully developed for the detection of organophosphorus pesticide residues. The results showed that the M-F-MWCNTs could effectively remove the interfering substances in Lycium ruthenicum Murr. (L. ruthenicum) samples. The recoveries of 10 tested targets were 74.9% to 113.5% with the relative standard deviations (RSDs) of 3.9-14.7%. The experiment results pointed out that the M-F-MWCNTs were qualified as QuEChERS clean-up materials and expected to be applied to other complex matrix samples and pesticide targets.

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Fluorescence methods are important tools to identify RNA-binding small molecules and further employed to study RNA-protein interactions. Most reported fluorescence strategies are based on covalent labeling of ligand or RNA, which can impede the binding between them to some extent, or light-off fluorescent indicator displacement methods, which ask for particular indicators. Herein, a label-free fluorescence strategy based on the light-on aggregation-induced emission (AIE) feature of tetraphenylethene (TPE) derivative to screen RNA-binding small molecules is presented. As a result of electrostatic interaction, the selected peptides can induce self-assembly of the TPE derivative to produce strong fluorescent emission; when the peptides are bound to RNA molecules, the TPE derivative is in the deaggregated form and shows no or minimum fluorescence. Based on the phenomenon, a competitive displacement assay combined with the TPE reporter was employed to characterize selected small molecules for their binding abilities to HIV-I RNAs. This AIE feature enables the fluorescence-off state of the TPE derivative in the presence of RNA-peptide complex to be "lightened up" quickly as the RNA-binding molecule is introduced and the peptide is competitively released. This strategy was carried out to test several small molecule binders, and the results are consistent with previous reports. This report gives an inspiring example of AIE-based fluorescent assay for HIV-I RNA-binding molecule screening, which may further be explored to build a drug screening platform for RNA-protein interference.

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Adenosine triphosphate (ATP) is the main energy currency of life that plays a vital role in supporting physiological activities in living organisms, including humans. Therefore, accurate and sensitive detection of ATP concentration is necessary in biochemical research and clinical diagnosis. Herein, a ratiometric fluorescence aptasensor was developed for ATP detection. A dual-function DNA strand comprising an ATP-binding aptamer (ABA) and berberine-binding aptamer (BBA) was designed and optimized, in which ABA can capture ATP and thioflavin T (ThT), whereas BBA can capture berberine. Interestingly, the fluorescence intensity of both berberine and ThT were enhanced as they were captured by this dual-function DNA strand. In the presence of ATP, the ABA on the 3'-end of the DNA bound specifically to its target, causing ThT release and a significant drop in ThT fluorescence. However, ATP had no significant effect on the interaction between berberine and DNA, remaining the enhanced fluorescence intensity of berberine stable. Based on this interesting phenomenon, a ratiometric fluorescence sensor was constructed that used the enhanced fluorescence intensity of berberine as reference to measure the fluorescence intensity of ThT for ATP detection. This ratiometric fluorescence strategy had excellent selectivity and high sensitivity towards ATP with a detection limit (3σ) as low as 24.8 nM. The feasibility of application of this method in biological samples was evaluated in human serum and urine samples, where it exhibited a good detection performance.

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The application of the dye-labeled fluorescence method in a ligand-RNA interaction assay is a complex and costly process prone to steric hindrance. Fluorescent nanomaterials offer an attractive alternative due to their simple, low-cost synthesis and effective screening properties. Here, CdTe@ZIF-8 core-shell nanocomposites were used as fluorescence signal transducer in the ligand-TAR RNA interaction assay. Different experimental strategies were developed based on the size-selective nature of the CdTe@ZIF-8 nanocomposites. When ligands can quench fluorescence, two assays of fluorescence recovery with TAR RNA and Tat peptide competitive displacement are carried out successively, which can not only distinguish ligands binding to TAR RNA but also screen potential Tat protein antagonists. When ligands cannot quench fluorescence, the mitoxantrone-TAR RNA complex is used in the competitive displacement assay. Ligands that displaced mitoxantrone from the mitoxantrone-TAR RNA complex signaled the interaction with TAR RNA. Eight ligands, including known and unknown TAR RNA-binding ligands, were tested via the above strategies. The results showed that this method was effective at distinguishing the known RNA-binding partner and screening the Tat antagonist from the test ligands. This simple and effective strategy is expected to be suitable for actual drug screening. Graphical abstract.

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With proper design, immobilization can be useful tool to improve the stability of enzymes, and in certain cases even their activity, selectivity, productivity and economic viability. An immobilized ß-glucosidase (BGL, EC 3.2.1.21) through matrix adsorption and cross-linked enzyme aggregate (ad-CLEA) technology is presented in this work. After adsorption and precipitation, BGL was immobilized to poly(glycidyl methacrylate-co-ethylenedimethacrylate) (PGMA/EDMA) microparticles using glutaraldehyde as the cross-linker. Immobilized BGL exhibits lower apparent Km but much higher Vmax than that of the soluble enzyme, suggesting greater enzyme-substrate affinity and rapid velocity. Besides, ad-CLEA-BGL presents better thermostability retaining activity nearly 70% for 3 h and approximately 50% for 5 h at 70 °C, high operational reusability remaining more than 90% activity after nine uses and excellent storage stability holding about 95% activity after 45 days. Furthermore, the cellobiose is completely hydrolyzed within 1 h with ad-CLEA-BGL, which is significantly more efficient than soluble enzyme (about 4 h). Therefore, BGL was successfully immobilized on PGMA/EDMA microparticles with an ad-CLEA technology and the immobilization greatly enhances the biochemical characteristics. This work indicates promising application for ad-CLEA-BGL in utilizing agricultural remnants, bio-converting cellobiose to fermentable reducing sugar and ethanol production.

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Using the commercially available and economical 6-hydroxycoumarin (6-HC) as the substrate, a dual-emission ratiometric fluorescence sensor was developed to detect tyrosinase (TYR) activity based on 3-aminophenyl boronic acid functionalized quantum dots (APBA-QDs). TYR can catalyze 6-HC, a monohydroxy compound, to form a fluorescence-enhancing o-hydroxy compound, 6,7-dihydroxycoumarin. Owing to the special covalent binding between the o-hydroxyl and boric acid groups, APBA-QDs react with 6,7-dihydroxycoumarin to form a five-membered ring ester dual-emission fluorescence probe for TYR. With an increase in TYR activity, the fluorescence at 675 nm originating from the QDs is gradually quenched, whereas that at 465 nm owing to 6,7-dihydroxycoumarin increases. Referencing the decreasing signal of the dual-emission probe at 675 nm to measure the increasing signal at 465 nm, a ratiometric fluorescence method was established to detect the TYR activity with high sensitivity and selectivity. Under the conditions optimized via response surface methodology, a linear range of 0-0.05 U/mL was obtained for the TYR activity. The detection limit was as low as 0.003 U/mL. This sensing strategy can also be adopted for the rapid screening of the TYR inhibitors.

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A bionic-compound-eye structure (BCES), which is a substitute of a microlens array, is proposed to enhance the performance of integral imaging (II) 3D display systems. Hexagonal ocelli without gaps and barriers are predesigned to obtain a continuous image, high-resolution, and uniform parallax. A curved substrate is designed to enhance the viewing angle. In addition, ocelli are fused with the substrate to form a relief structure, BCES. When they are placed above a normal display, continuous and full-parallax 3D images with 150 µm effective resolution and a 28° horizontal, 22° vertical viewing angle could be achieved, about twice as much as that of normal systems. The weight of the BCES is 31 g, and the thickness of the whole system is 22 mm; thus, the BCES-based II (BCES-II) is very compact. In addition, this structure can be easily integrated into a cell phone or iPad for compact quasi-2D and 3D adjustable display.

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Chemotherapy still accounts for a large proportion of the treatments of tumors, but the drug resistance and side effects caused by long-term chemotherapy should not be underestimated. In this work, the drug combination strategy has been widely developed to overcome the side effects brought by the use of single drugs and improve the therapeutic effect. However, in clinical applications, the co-delivery of drugs is very difficult, and different in vivo kinetics due to different drug properties will lead to a decrease in efficacy. Thus, the design of novel antitumor therapeutic agents, including new platinum agents, represents an area in need of urgent attention. Our investigation implies a promising strategy for the design of a platinum prodrug to enhance the treatment of breast cancer. A dual-drug delivery nanoparticle was developed for enhanced treatment of breast cancer based on a two-into-one co-delivery strategy. Through the synergistic effect of released cisplatin hydrate and tolfenamic acid (COX-2 inhibitor) from the coordination prodrug, the tumor growth is significantly suppressed, and the survival time is greatly extended in breast tumor-bearing mice.

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