Targeting the PHF8/YY1 axis suppresses cancer cell growth through modulation of ROS.

High levels of mitochondrial reactive oxygen species (mROS) are linked to cancer development, which is tightly controlled by the electron transport chain (ETC). However, the epigenetic mechanisms governing ETC gene transcription to drive mROS production and cancer cell growth remain to be fully characterized. Here, we report that protein demethylase PHF8 is overexpressed in many types of cancers, including colon and lung cancer, and is negatively correlated with ETC gene expression. While it is well known to demethylate histones to activate transcription, PHF8 demethylates transcription factor YY1, functioning as a co-repressor for a large set of nuclear-coded ETC genes to drive mROS production and cancer development. In addition to genetically ablating PHF8, pharmacologically targeting PHF8 with a specific chemical inhibitor, iPHF8, is potent in regulating YY1 methylation, ETC gene transcription, mROS production, and cell growth in colon and lung cancer cells. iPHF8 exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo. Our data uncover a key epigenetic mechanism underlying ETC gene transcriptional regulation, demonstrating that targeting the PHF8/YY1 axis has great potential to treat cancers.

Gamma-Aminobutyric Acid Enhances Cadmium Phytoextraction by Coreopsis grandiflora by Remodeling the Rhizospheric Environment.

Gamma-aminobutyric acid (GABA) significantly affects plant responses to heavy metals in hydroponics or culture media, but its corresponding effects in plant-soil systems remain unknown. In this study, different GABA dosages (0-8 g kg-1) were added to the rhizosphere of Coreopsis grandiflora grown in Cd-contaminated soils. Cd accumulation in the shoots of C. grandiflora was enhanced by 38.9-159.5% by GABA in a dose-dependent approach because of accelerated Cd absorption and transport. The increase in exchangeable Cd transformed from Fe-Mn oxide and carbonate-bound Cd, which may be mainly driven by decreased soil pH rather than GABA itself, could be a determining factor responsible for this phenomenon. The N, P, and K availability was affected by multiple factors under GABA treatment, which may regulate Cd accommodation and accumulation in C. grandiflora. The rhizospheric environment dynamics remodeled the bacterial community composition, resulting in a decline in overall bacterial diversity and richness. However, several important plant growth-promoting rhizobacteria, especially Pseudomonas and Sphingomonas, were recruited under GABA treatment to assist Cd phytoextraction in C. grandiflora. This study reveals that GABA as a soil amendment remodels the rhizospheric environment (e.g., soil pH and rhizobacteria) to enhance Cd phytoextraction in plant-soil systems.

Mutation of barley HvPDIL5-1 improves resistance to yellow mosaic virus disease without growth or yield penalties.

The soil-borne yellow mosaic virus disease, which is caused by the bymoviruses barley yellow mosaic virus (BaYMV) and/or barley mild mosaic virus (BaMMV), seriously threatens winter barley production in Europe and East Asia. Both viruses are transmitted by the soil-borne plasmodiophorid Polymyxa graminis and are difficult to eliminate through chemical or physical measures in the field, making breeding for resistant cultivars the optimal strategy for disease control. The resistance locus rym1/11 was cloned encoding the host factor gene Protein Disulfide Isomerase Like 5-1 (PDIL5-1), whose loss-of-function variants confer broad-spectrum resistance to multiple strains of BaMMV/BaYMV. Most resistance-conferring variants have been identified in six-rowed barley landraces/historic cultivars, and their introgression into modern two-rowed malting cultivars is difficult because PDIL5-1 is located in a peri-centromeric region with suppressed recombination. In this study, we used CRISPR/Cas9 genome editing to modify PDIL5-1 in the BaYMV/BaMMV-susceptible elite malting barley cv. 'Golden Promise' and obtained the mutants pdil5-1-a and pdil5-1-b. PDIL5-1 in the pdil5-1-a mutant encodes a protein lacking a cysteine residue, and pdil5-1-b contains a protein-coding frameshift. Both mutants were completely resistant to BaYMV. The knockout mutant pdil5-1-b showed complete BaMMV resistance, while pdil5-1-a showed decreased viral accumulation but no disease symptoms if compared to 'Golden Promise'. Both PDIL5-1 edited lines, as well as the previously produced EMS-induced pdil5-1 mutant '10253-1-5' in the elite malting barley cv. 'Barke' background, displayed no growth or yield penalties in garden experiments or bymovirus-free field trials. Line '10253-1-5' showed improved resistance and yield performance compared to the wild-type and its sibling line when grown in infectious fields. Therefore, genome editing of the host factor gene PDIL5-1 could facilitate the breeding of barley varieties with resistance to bymoviruses.

Design and synthesis of N-(1-(6-(substituted phenyl)-pyridazin-3-yl)-piperidine-3-yl)-amine derivatives as JMJD6 inhibitors.

JMJD6 is a member of the JmjC domain-containing family and has been identified as a promising therapeutic target for treating estrogen-induced and triple-negative breast cancer. To develop novel anti-breast cancer agents, we synthesized a class of N-(1-(6-(substituted phenyl)-pyridazine-3-yl)-piperidine-3-yl)-amine derivatives as potential JMJD6 inhibitors. Among them, the anti-cancer compound A29 was an excellent JMJD6 binder (KD = 0.75 ± 0.08 µM). It could upregulate the mRNA and protein levels of p53 and its downstream effectors p21 and PUMA by inhibiting JMJD6. Besides, A29 displayed potent anti-proliferative activities against tested breast cancer cells by the induction of cell apoptosis and cell cycle arrest. Significantly, A29 also promoted a remarkable reduction in tumor growth, with a TGI value of 66.6% (50 mg/kg, i.p.). Taken together, our findings suggest that A29 is a potent JMJD6 inhibitor bearing a new scaffold acting as a promising drug candidate for the treatment of breast cancer.

Polyaspartic acid enhances the Cd phytoextraction efficiency of Bidens pilosa by remolding the rhizospheric environment and reprogramming plant metabolism.

The green soil chelator polyaspartic acid (PASP) can enhance heavy metal phytoextraction efficiency, but the potential mechanisms are not clearly understood from the whole soil-plant system. In this study, we explored the effects and potential mechanisms of PASP addition in soils on plant growth and cadmium (Cd) uptake in the Cd hyperaccumulator Bidens pilosa by analysing variations in chemical elements, rhizospheric microbial community, and plant metabolomics. The results showed that PASP significantly promoted the biomass yield and Cd concentration in B. pilosa, leading to an increase in the total accumulated Cd by 46.4% and 76.4% in shoots and 124.7% and 197.3% in roots under 3 and 6 mg kg-1 PASP addition, respectively. The improved soil-available nutrients and enriched plant growth-promoting rhizobacteria (e.g., Sphingopyxis, Sphingomonas, Cupriavidus, Achromobacter, Nocardioides, and Rhizobium) were probably responsible for the enhanced plant growth after PASP addition. The increase in Cd uptake by plants could be due to the improved rhizosphere-available Cd, which was directly activated by PASP and affected by the induced rhizobacteria involved in immobilizing/mobilizing Cd (e.g., Sphingomonas, Cupriavidus, Achromobacter, and Rhizobium). Notably, PASP and/or these potassium (K)-solubilizing rhizobacteria (i.e., Sphingomonas, Cupriavidus, and Rhizobium) highly activated rhizosphere-available K to enhance plant growth and Cd uptake in B. pilosa. Plant physiological and metabolomic results indicated that multiple processes involving antioxidant enzymes, amino acids, organic acids, and lipids contributed to Cd detoxification in B. pilosa. This study provides novel insights into understanding how soil chelators drive heavy metal transfer in soil-plant systems.

Physiological and rhizospheric response characteristics to cadmium of a newly identified cadmium accumulator Coreopsis grandiflora Hogg. (Asteraceae).

Screening for superior cadmium (Cd) phytoremediation resources and uncovering the mechanisms of plant response to Cd are important for effective phytoremediation of Cd-polluted soils. In this study, the characteristics of Coreopsis grandiflora related to Cd tolerance and accumulation were analyzed to evaluate its Cd phytoremediation potential. The results revealed that C. grandiflora can tolerate up to 20 mg kg-1 of Cd in the soil. This species showed relatively high shoot bioconcentration factors (1.09-1.85) and translocation factors (0.46-0.97) when grown in soils spiked with 5-45 mg kg-1 Cd, suggesting that C. grandiflora is a Cd accumulator and can potentially be used for Cd phytoextraction. Physiological analysis indicated that antioxidant enzymes (i.e., superoxide dismutase, peroxidase, and catalase) and various free amino acids (e.g., proline, histidine, and methionine) participate in Cd detoxification in C. grandiflora grown in soil spiked with 20 mg kg-1 of Cd (Cd20). The overall microbial richness and diversity remained similar between the control (Cd0) and Cd20 soils. However, the abundance of multiple rhizospheric microbial taxa was altered in the Cd20 soil compared with that in the Cd0 soil. Interestingly, many plant growth-promoting microorganisms (e.g., Nocardioides, Flavisolibacter, Rhizobium, Achromobacter, and Penicillium) enriched in the Cd20 soil likely contributed to the growth and vitality of C. grandiflora under Cd stress. Among these, some microorganisms (e.g., Rhizobium, Achromobacter, and Penicillium) likely affected Cd uptake by C. grandiflora. These abundant plant growth-promoting microorganisms potentially interacted with soil pH and the concentrations of Cd and AK in soil. Notably, potassium-solubilizing microbes (e.g., Rhizobium and Penicillium) may effectively solubilize potassium to assist Cd uptake by C. grandiflora. This study provides a new plant resource for Cd phytoextraction and improves our understanding of rhizosphere-associated mechanisms of plant adaptation to Cd-contaminated soil.

Discovery of new chalone adamantyl arotinoids having RXRα-modulating and anticancer activities.

In the present study, a new series of chalcone adamantly arotinoids (chalcone AdArs) derived from RAR antagonist MX781, are synthesized, characterized, and evaluated for the biological activities in vitro. The studies of antiproliferative activity and RXRα-binding affinity of target compounds result in the discovery of a lead candidate (WA15), which is a good RXRα binder (Kd = 2.89 × 10-6 M) with potent antiproliferative activity against human cancer cell lines (IC50 ≈ 10 µM) and low toxic to normal LO2 and MRC-5 cells (IC50 > 50 µM). Different from MX781, WA15 eliminates RARα antagonist activity but inhibits 9-cis-RA-induced RXRα transactivation activity in a dose-dependent manner. Compound WA15 is found to be a good apoptosis inducer in various cancer cells and promotes cell apoptosis in an RXRα-independent manner. Besides, WA15 shows the induction of proteasome-dependent RXRα degradation which might enhance the WA15-induced apoptosis. Finally, the immunoblotting indicates that WA15 can inhibit the TNFα-induced IKK activation and IκBα degradation, suggesting that the anticancer activity of WA15 might be related to the inhibition of IKK/NF-κB signal pathway.

[Cadmium Accumulation Characteristics of Four Herbs].

A pot-based experiment was conducted to study the Cd tolerance and accumulation characteristics of four invasive herbs (Galinsoga quadriradiata, Panicum dichotomiflorum, Setaria geniculata, and Lolium persicum) under exposures of 0 (T0), 5 (T5), 25 (T25), and 50 mg·kg-1 (T50) soil Cd concentrations to screen for potential Cd accumulators for phytoremediation. The results showed that the biomasses of both shoots and roots of G. quadriradiata had no significant changes compared to the control (T0) samples under all Cd treatments, whereas the biomass of the other three Poaceae species significantly decreased under the T25 or T50 treatment. The results indicate that G. quadriradiata had stronger Cd tolerance than the other three species. The Cd concentrations in the shoots and roots of the four herbs significantly increased with an increase in soil Cd concentrations, but the shoot bioconcentration factors (SBCF) of the four plant species significantly decreased under T5, T25, and T50 treatment. The SBCF of G. quadriradiata and P. dichotomiflorum were greater than 1 whereas those of S. geniculata and L. persicum were lower than 1. The translocation factors (TF) of G. quadriradiata were 0.93, 0.73, and 1.04 under T5, T25, and T50 treatment, respectively, which were significantly higher than those of the other three plants under the same soil Cd concentration. In addition, both the total Cd and shoot Cd contents of G. quadriradiata were notably higher than in the other three species under the same Cd treatment. Moreover, 90% of the Cd in G. quadriradiata could be transferred aboveground, which was significantly higher than for the other three plants. Based on our comprehensive comparison of Cd tolerance and accumulation capacity, we suggest that G. quadriradiata is a high-Cd accumulator with considerable phytoremediation potential.

Combined transcriptomic, proteomic and biochemical approaches to identify the cadmium hyper-tolerance mechanism of turnip seedling leaves.

Cadmium (Cd) pollution is a prominent environment problem, and great interests have been developed towards the molecular mechanism of Cd accumulation in plants. In this study, we conducted combined transcriptomic, proteomic and biochemical approaches to explore the detoxification of a Cd-hyperaccumulating turnip landrace exposed to 5 µM (T5) and 25 µM (T25) Cd treatments. A total of 1090 and 2111 differentially expressed genes (DEGs) and 161 and 303 differentially expressed proteins (DEPs) were identified in turnips under T5 and T25, respectively. However, poor correlations were observed in expression changes between mRNA and protein levels. The enriched KEGG pathways of DEGs with a high proportion (> 80%) of upregulated genes were focused on the flavonoid biosynthesis, sulphur metabolism and glucosinolate biosynthesis pathways, whereas those of DEPs were enriched on the glutathione metabolism pathway. This result suggests that these pathways contribute to Cd detoxification in turnips. Furthermore, induced antioxidant enzymes, heat stock proteins and stimulated protein acetylation modification seemed to play important roles in Cd tolerance in turnips. In addition, several metal transporters were found responsible for the Cd accumulation capacity of turnips. This study may serve as a basis for breeding low-Cd-accumulating vegetables for foodstuff or high-Cd-abstracting plants for phytoremediation.

Xuebijing injection in the treatment of COVID-19: a retrospective case-control study.

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-α. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-α and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.

Design, synthesis and biological evaluation of methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold: Novel potential CDK9 inhibitors.

In continuation of our previous work on the investigation of CDK9 inhibitors bearing indole moiety for the discovery of novel anticancer agents, novel methylenehydrazine-1-carboxamide derivatives with (5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)-1H-indole scaffold were designed, synthesized, and evaluated for the CDK9 inhibitory activity and anticancer activity. Biological activity results demonstrated that most of these derivatives possessed good inhibitory on the kinase activity of CDK9 such as blocking its phosphorylation function and inhibiting HIV-1 transcription. Compound 12i was found to be the most potent CDK9 inhibitor and exhibited excellent anticancer activity against HepG2, A375, MCF-7, and A549, but low toxic on normal cells including HaCaT and MCF-10A. Further studies revealed that as a result of CDK9 inhibition and subsequent inhibition of phosphorylation at Serine 2 of the RNAPII CTD, the representative compound 12i dose-dependently increased cleaved PARP level, exerting its antiproliferative effect through induction of apoptosis in cancer cells. Finally, the molecular docking analysis implied that 12i had a good binding affinity with CDK9. In summary, 12i is a potent CDK9 inhibitor and can be considered as a good lead-candidate for developing potential anticancer drugs.

Clinical features and treatment of COVID-19 patients in northeast Chongqing.

The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.

Effects of soil properties on accumulation characteristics of copper, manganese, zinc, and cadmium in Chinese turnip.

Clarifying the mechanisms of heavy metal (HM) accumulation and translocation from soil-root-leaf is crucial to coping with soil HM pollution. In this study, we analysed copper (Cu), manganese (Mn), zinc (Zn) and cadmium (Cd) accumulation characteristics in Chinese turnips and the effect of soil physicochemical properties on both HM accumulation and translocation. Our results indicate that Chinese turnips absorb and translocate Mn, Zn, and Cd at much higher levels than they do Cu. When we measured bioconcentration factors in Chinese turnips for different HMs in the same soil, we found Chinese turnip capacities for HM accumulation decrease from Zn > Mn > Cd > Cu. In addition, the translocation factor for these HMs decreases from Mn > Cd > Zn > Cu. Correlation analysis indicates that soil pH and various soil components are either negatively or positively correlated with Mn, Zn, and Cd accumulation; also, soil properties are correlated with Mn translocation from root to leaf. These findings may help evaluate HM accumulation and translocation mechanisms as well as artificially regulate HM uptake levels from soils to turnips.

Physiological and biochemical analysis of mechanisms underlying cadmium tolerance and accumulation in turnip.

The capacity of plants to accumulate cadmium (Cd) is significant for phytoremediation of Cd-polluted soils. Turnips cultivated in China include species featuring high Cd accumulation and some of these plants act as Cd hyperaccumulator landraces. These plants can accumulate over 100 mg Cd kg-1 dry weight in leaves without injury. Hence, studies that explore mechanisms underlying Cd detoxification and transport in turnip plants are essential. In the present study, we compared physiological and biochemical changes in turnip leaves treated with two Cd concentrations to controls. We discovered that Cd stress significantly increased the enzymatic activities or compound contents in the antioxidant system, including members of the glutathione-ascorbic acid cycle, whereas oxidation of reactive oxygen species (ROS) remained stable. Cd treatments also increased the contents of phytochelatins as well as a number of amino acids. Based on these results, we conclude that turnips initiate a series of response processes to manage Cd treatment. First, the antioxidant system maintaining ROS homeostasis and osmotic adjustment is excited to maintain stability of cell osmotic potential. Cd is chelated into its stable form to reduce its toxicity. Cd is possibly transported to vacuoles or non-protoplasts for isolation. Amino acid synthesis may directly and indirectly play an important role in these processes. This study partly revealed physiological and biochemical mechanisms underlying turnip response to Cd stress and provides information on artificially increasing or decreasing Cd accumulation in turnips and other plants.

Cadmium phytoremediation potential of turnip compared with three common high Cd-accumulating plants.

Phytoextraction is a phytoremediation technique used for remediating polluted soils and it greatly relies on the plants' capacities to accumulate contaminants. Turnip is a high cadmium (Cd)-accumulating plant. We compared the Cd tolerance, growth, and Cd accumulation characteristics of two turnip landraces with three additional commonly known high Cd-accumulating species to systematically estimate its Cd phytoremediation potential. Results showed that the turnips could tolerate relatively lower Cd concentrations than other plants. Growth characteristics analyses indicated that the turnips initially grew rapidly and then gradually slowed down, and their photosynthetic parameters indicated that biomass accumulation was easily affected by light. However, the Cd uptake and translocation capacities of the two turnip landraces were higher than those of Phytolacca americana Linn. and Bidens pilosa Linn. but close to that of Brassica napus Linn.. Ultimately, large amounts of Cd accumulated in turnips during early growth and slightly increased as the fleshy roots increased in size. Based on these findings, the present turnip landraces have potential for soil remediation, but additional research is needed before these landraces can be practically used. Moreover, turnips are good candidates for studying the molecular mechanism of high Cd accumulation in plants.

Cadmium Accumulation Characteristics in Turnip Landraces from China and Assessment of Their Phytoremediation Potential for Contaminated Soils.

Heavy metal (HM) pollution is a global environmental problem that threatens ecosystem and human health. Cadmium (Cd) pollution is the most prominent HM pollution type because of its high toxicity, strong migration, and the large polluted area globally. Phytoremediation of contaminated soil is frequently practiced because of its cost-effectiveness and operability and because it has no associated secondary pollution. High-accumulation plants, including those identified as hyperaccumulators, play an important role in phytoremediation. Therefore, screening of plants to identify hyperaccumulators is important for continued phytoremediation. In the present study, we investigated the Cd tolerance and accumulation capabilities of 18 turnip landraces from China under a soil experiment with known Cd level. The results indicated that turnip has a high capacity for Cd accumulation. Furthermore, significant differences in Cd tolerance and accumulation characteristics were found among different landraces when they grew at 50 mg kg-1 (dry weight) Cd concentration. Among the studied landraces, five turnip landraces met the requirements of Cd hyperaccumulators and three landraces were identified as potential candidates. However, the total Cd content accumulated by individual plant of different turnip landraces was dependent on both the Cd accumulation capacity and plant biomass. Compared with some reported Cd hyperaccumulators, turnip not only shows a high Cd-accumulation capacity but also has rapid growth and a wide distribution area. These advantages indicate that turnip may have considerable potential for phytoremediation of Cd-contaminated soil. Furthermore, the study also indicates that it is not advisable to consume turnip cultivated in an environment that exceeds safe Cd levels.

Are PEGylated liposomes better than conventional liposomes? A special case for vincristine.

Cancer poses a significant threat to human health worldwide, and many therapies have been used for its palliative and curative treatments. Vincristine has been extensively used in chemotherapy. However, there are two major challenges concerning its applications in various tumors: (1) Vincristine's antitumor mechanism is cell-cycle-specific, and the duration of its exposure to tumor cells can significantly affect its antitumor activity and (2) Vincristine is widely bio-distributed and can be rapidly eliminated. One solution to these challenges is the encapsulation of vincristine into liposomes. Vincristine can be loaded into conventional liposomes, but it quickly leak out owing to its high membrane permeability. Numerous approaches have been attempted to overcome this problem. Vincristine has been loaded into PEGylated liposomes to prolong circulation time and improve tumor accumulation. These liposomes indeed prolong circulation time, but the payout characteristic of vincristine is severer, resulting in a compromised outcome rather than a better efficacy compared to conventional sphingomyelin (SM)/cholesterol (Chol) liposomes. In 2012, the USA Food and Drug Administration (FDA) approved SM/Chol liposomal vincristine (Marqibo®) for commercial use. In this review, we mainly focus on the drug's rapid leakage problem and the potentially relevant solutions that can be applied during the development of liposomal vincristine and the reason for conventional liposomal vincristine rather than PEGylated liposomes has access to the market.