Silencing LY6D Expression Inhibits Colon Cancer in Xenograft Mice and Regulates Colon Cancer Stem Cells' Proliferation, Stemness, Invasion, and Apoptosis via the MAPK Pathway.

This study explored the role of lymphocyte antigen 6 family member D (LY6D) in colon cancer stem cells' (CCSCs) proliferation and invasion. LY6D was knocked down using siRNA, and the down-regulation of LY6D was verified using Western blotting. After LY6D knockdown, CCSCs' proliferation, stemness, and invasion were suppressed, whereas apoptosis was increased. Gene Ontology (GO) enrichment analysis revealed that the differentially expressed genes (DEGs) between siLY6D and the negative control groups were significantly enriched in the cell-substrate adherens junction, focal adhesion, and cell-substrate junction terms. Meanwhile, the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DEGs were significantly enriched in the MAPK pathway. In addition, Western blotting results showed that pBRAF and pERK1/2, cascade kinases of the MAPK pathway, were significantly down-regulated after LY6D knockdown. In addition, nude mice xenograft experiments showed that the siLY6D treatment decreased tumor sizes and weights and improved tumor-bearing mice survival rates compared with the control group. In conclusion, these findings indicate that LY6D, which is highly expressed in CCSCs, is a key factor involved in tumor growth and development and might be a potential cancer marker and therapeutic target for colon cancer.

TaNRAMP3 is essential for manganese transport in Triticum aestivum.

Manganese (Mn) is an essential trace element for almost all living organisms. In plants, Mn deficiency, which is occurs in calcareous soils or alkaline soils, severely limiting crop yields. However, the potential mechanism of Mn transport in Triticum aestivum is still obscure. Here, we found that TaNRAMP3, a member of the naturally resistant macrophage protein (NRAMP) family in Triticum aestivum, is located in the plasma membrane of protoplasts and functions as an influx transporter for Mn in yeast (Δsmf1). The expression of TaNRAMP3 was induced under Mn-deficiency conditions. Furthermore, TaNRAMP3-RNAi plants exhibited a sensitive phenotype, while transgenic plants overexpressing TaNRAMP3 showed a tolerant phenotype. In addition, TaNRAMP3 rescued the sensitive phenotype of Arabidopsis nramp1 mutant under Mn deficiency condition. In summary, our study reveals the key role of TaNRAMP3 in Mn transport in Triticum aestivum, allowing it to adapt to Mn-deficiency stress. These findings provide new insights for the cultivation of Mn-deficiency tolerant wheat varieties.

Studies on the Light-Induced Phase Transition of CsPbBr3 Metal Halide Perovskite Materials.

We investigate the internal mechanism of the light-induced phase transition of CsPbBr3 perovskite materials via density functional theory simulations. Although CsPbBr3 tends to appear in the orthorhombic structure, it can be changed easily by external stimulus. We find that the transition of photogenerated carriers plays the decisive role in this process. When the photogenerated carriers transit from the valence band maximum to conduction band minimum in the reciprocal space, they actually transit from Br ions to Pb ions in the real space, which are taken away by the Br atoms with higher electronegativity from Pb atoms during the initial formation of the CsPbBr3 lattice. The reverse transition of valence electrons leads to the weakening of bond strength, which is proved by our calculated Bader charge, electron localization function, and integral value of COHP results. This charge transition releases the distortion of the Pb-Br octahedral framework and expands the CsPbBr3 lattice, providing possibilities to the phase transition from the orthorhombic structure to tetragonal structure. This phase transition is a self-accelerating positive feedback process, increasing the light absorption efficiency of the CsPbBr3 material, which is of great significance for the widespread promotion and application of the photostriction effect. Our results are helpful to understand the performance of CsPbBr3 perovskite under a light irradiation environment.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported. AIM OF THE STUDY: To search for new anti-neuro-inflammatory compounds from the leaves of C. minax and elucidate their mechanism on anti-neuroinflammatory effect. MATERIALS AND METHODS: The main metabolites of the ethyl acetate fraction from C. minax were analyzed and purified via HPLC and various column chromatography techniques. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and single crystal X-ray diffraction analysis. Anti-neuroinflammatory activity was evaluated in BV-2 microglia cells induced by LPS. The expression levels of molecules in NF-κB and MAPK signaling pathways were analyzed through western blotting. Meanwhile, the time- and dose-dependent expression of associated proteins such as iNOS and COX-2 were detected by western blotting. Furthermore, Compounds 1 and 3 were performed on the NF-κB p65 active site using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: 20 cassane diterpenoids, including two novel ones (caeminaxins A and B) were isolated from the leaves of C. minax Hance. Caeminaxins A and B possessed a rare unsaturated carbonyl moiety in their structures. Most of the metabolites exhibited potent inhibition effects with IC50 values ranging from 10.86 ± 0.82 to 32.55 ± 0.47 µM. Among them, caeminaxin A inhibited seriously the expression of iNOS and COX-2 proteins and restrained the phosphorylation of MAPK and the activation of NF-κB signaling pathways in BV-2 cells. The anti-neuro-inflammatory mechanism of caeminaxin A has been studied systematically for the first time. Furthermore, biosynthesis pathways for compounds 1-20 were discussed. CONCLUSIONS: The new cassane diterpenoid, caeminaxin A, alleviated the expression of iNOS and COX-2 protein and down-regulated of intracellular MAPK and NF-κB signaling pathways. The results implied that cassane diterpenoids had potential to be developed into therapeutic agents for neurodegenerative disorders such as Alzheimer's disease.

Discovery of indole-piperazine derivatives as selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting activities and neuroprotective activities.

Novel indole-piperazine derivatives with a hydroxamic acid moiety were designed and synthesized as selective histone deacetylase 6 (HDAC6) inhibitors. In enzymatic assays, all compounds exhibited nanomolar IC50 values. N-hydroxy-4-((4-(7-methyl-1H-indole-3-carbonyl)piperazin-1-yl)methyl)benzamide, 9c, was the most potent HDAC6 inhibitor (IC50, 13.6 nM). In vitro, 9c induced neurite outgrowth of PC12 cells without producing toxic effects, better than Tubastatin A (Tub A). Additionally, 9c demonstrated blatant neuroprotective activity in PC12 cells against H2O2-induced oxidative damage. In western blot assay, 9c could increase the acetylation of α-tubulin in a dose-dependent manner.

Bistable insulin response: The win-win solution for glycemic control.

To satisfy both the safety and rapidity of glycemic control, muscles' insulin response must be bistable, as theoretically predicted. Here, we test the bistability hypothesis by combining cellular experiments (to measure the threshold values in vitro) with mathematical modeling (to test the relevance of bistability in vivo). We examine bistability in C2C12 myotubes by both single-cell analysis (FÓ§rster resonance energy transfer) and cultured cells analysis (immunoblot). These technologies demonstrate bistable insulin response, with typical switch-on and switch-off thresholds of approximately 300 and 100 pM, respectively. Our mathematical model demonstrates the indispensability of bistability in interpreting experimental data, reveals fine details of plasma glucose-insulin dynamics, and explains unclear phenomena. These results suggest that the body's ability to simultaneously avoid both hypoglycemia and hyperglycemia is mediated by bistability. The switch-on threshold is a promising biomarker for metabolic complications due to its deep quantitative connection with body composition, which is easy to measure.

Highly oxygenated chemical constitutes and rearranged derivatives with neurotrophic activity from Ganoderma cochlear.

ETHNOPHARMACOLOGICAL RELEVANCE: The morphological characteristics of Ganoderma cochlear (Blume & T. Nees) Bres were identical to G. sinsense J.D. Zhao, L.W. Hsu & X.Q. Zhang, however, with the fungus stipe lying in the back of the pileus. Fruiting bodies and spores of G. cochear have been traditionally used for smoothing, sleeping improvement, memory impairment, anti-aging, and prolonging life. Alzheimer's disease (AD) is a chromic progressive neurodegenerative disorder associated with loss of memory and cognition. Hallmarks of AD include aging, amyloid-ß plaques, neurofibrillary tangles, neuron loss, neuronal degeneration, network disruption, cognitive dysfunction, inflammation and oxidation stress. In this study, norlanostanoids from G. cochear are identified as potential neurotrophic chemists related to the memory impairment usage to slow down pathogenetic process and restore neural circuits for AD. AIM OF STUDY: Chemical and biological investigations in this study uncovered the potential constituents related to the traditional usage of G. cochlear. MATERIALS AND METHODS: The extract of the mushrooms was purified using various column chromatography techniques and high-performance liquid chromatography (HPLC). The structures of the isolates were elucidated by combination of spectral, and single crystal X-ray diffraction analysis. The neurotrophic activity was evaluated by the differentiation state of PC12 cells, and the dose-dependent and time-dependant expression of growth-associated protein (GAP-43) was analyzed by western blotting. RESULTS: Ganorbifates J-T (1-11), eleven previously undescribed triterpenoids together with five known trinorlanostanoids (12-16) were isolated from the fruiting bodies of G. Cochlear. Among them, ganorbifates N-O (5-6) had a demethylation at C-28 compared to the classic skeleton of 3,4-seco-25,26,27-trinorlanostanoids to form a new group of 3,4-seco-25,26,27,28-tetranorlanostanoids. Based on this, a novel skeleton of ganorbifate M (4) was further established by the arrangement of C-29 from C-4 to C-7. A plausible biosynthetic pathway of compounds 4-6 was proposed. Eight of the sixteen isolates showed neurotrophic activity with the concentration of 10 µM. Furthermore, compound 15 exhibited a dose-dependent neurogenic activity, and also strengthened the expression of the growth-associated protein (GAP-43) in NGF-induced PC-12 cells, whereas 11 showed an inhibitory effect at higher concentration. CONCLUSION: These results demonstrated that 3,4-seco-norlanostanoids had reliable potential in promoting the outgrowth of PC-12 cells and could be used in the prevention and treatment of Alzheimer's disease, which is consist with the beneficial effects of G. Cochlear.

Derivatives of sarcodonin A isolated from Sarcodon scabrosus reversed LPS-induced M1 polarization in microglia through MAPK/NF-κB pathway.

Emerging evidence suggests the regulation of microglial phenotype balance between M1 and M2 will be a potential therapeutic strategy for microglia-mediated neuroinflammation in Alzheimer's disease (AD). Herein, we evaluated the anti-neuroinflammatory effects and the underlying mechanism of a natural cyathane diterpenoid sarcodonin A (1) derived from the mushroom Sarcodon scabrosus and its six new derivatives (2-7). Lipopolysaccharide (LPS)-activated primary microglia and microglia cell lines were used as models. The nitrite test and immunostaining showed that the derivative named 6 was more effective in inhibiting neuroinflammation. qRT-PCR, ELISA, and western blotting revealed that 6 showed more significant suppression on mRNA and protein expression of proinflammatory M1 markers of TNF-α, IL-6, IL-1ß, iNOS, and COX-2, while more obvious potentiation on mRNA and protein levels of anti-inflammatory M2 markers of IL-10 and ARG-1. In mechanism, western blotting demonstrated that 6 inhibited LPS-induced activation of MAPK, and prevented LPS-stimulated nuclear translocation of NF-κB p65. Molecular docking revealed that 1 and 6 constructed interactions with iNOS. Collectively, the present study indicated that 1 and 6 might support neuroprotection by reversing LPS-induced microglia M1 polarization, implying that sarcodonin A can be a promising candidate for developing new therapeutics against AD by targeting microglia-mediated neuroinflammation.

A review of synthetic bioactive tetrahydro-ß-carbolines: A medicinal chemistry perspective.

1, 2, 3, 4-Tetrahydro-ß-carboline (THßC) scaffold is widespread in many natural products (NPs) and synthetic compounds which show a variety of pharmacological activities. In this article, we reviewed the design, structures and biological characteristics of reported synthetic THßC compounds, and structure and activity relationship (SAR) of them were also discussed. This work might provide a reference for subsequent drug development based on THßC.

Association of Insulin Resistance and ß-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients.

Background: The interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, ß-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism. Methods: A total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn, ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and ß-cell dysfunction (HOMA-%ß) were applied to elucidate the nexus between ß-C-terminal telopeptide (ß-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). ß-CTX, OC and P1NP were detected by chemiluminescence. Results: HOMA-IR was negatively associated with ß-CTX, P1NP and OC (regression coefficient (ß) -0.044 (-0.053, -0.035), Q4vsQ1; ß -7.340 (-9.130, -5.550), Q4vsQ1 and ß -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend <0.001). HOMA-%ß was positively associated with ß-CTX, P1NP and OC (ß 0.022 (0.014, 0.031), Q4vsQ1; ß 6.951 (5.300, 8.602), Q4vsQ1 and ß 1.361 (0.921, 1.800), Q4vsQ1, respectively, all P for trend <0.001). Conclusions: Our results support that lower bone turnover biomarker (ß-CTX, P1NP and OC) levels were associated with a combination of higher prevalence of insulin resistance and worse ß-cell function among dysglycemia patients. It is feasible to detect bone turnover in diabetes or hyperglycemia patients to predict the risk of osteoporosis and fracture, relieve patients' pain and reduce the expenses of long-term cure.

Does aspirin reduce the incidence, recurrence, and mortality of colorectal cancer? A meta-analysis of randomized clinical trials.

BACKGROUND: Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of all cancer deaths in the USA. Some evidences are shown that aspirin can reduce the morbidity and mortality of different cancers, including CRC. Aspirin has become a new focus of cancer prevention and treatment research so far; clinical studies, however, found conflicting conclusions of its anti-cancer characteristics. This study is to summarize the latest evidence of correlation between aspirin use and CRC and/or colorectal adenomas. METHODS: Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. The pooled relative risk (RR) with 95% confidence interval (CI) was used to estimate the effect of aspirin on colorectal cancer and/or colorectal adenomas. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: The result showed that aspirin use was not associated with incidence of CRC (RR 0.97; 95% CI 0.84-1.12; P = 0.66; I2 = 34%), aspirin use was found to be associated with reduced recurrence of colorectal adenomas (RR 0.83; 95% CI 0.72-0.95; P = 0.006; I2 = 63%) and reduced mortality of CRC (RR 0.79; 95% CI 0.64-0.97; P = 0.02; I2 = 14%). Subgroup analysis found a statistically significant association in low dose with a pooled RR of 0.85 (95% CI 0.74-0.99; P = 0.03; I2 = 31%). CONCLUSIONS: This meta-analysis of randomized controlled trial data indicates that aspirin reduces the overall risk of recurrence and mortality of CRC and/or colorectal adenomas. Incidence of CRC was also reduced with low-dose aspirin. The emerging evidence on aspirin's cancer protection role highlights an exciting time for cancer prevention through low-cost interventions. TRIAL REGISTRATION: Clinicaltrials.gov no: CRD42020208852; August 18, 2020; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020208852 ).

Discovery of 1,3-Disubstituted 2,5-Diketopiperazine Derivatives as Potent Class I HDACs Inhibitors.

Histone deacetylases (HDACs) as attractive targets in many diseases therapies has been studied extensively, and its application in cancer research is the most important. Here, we developed a series of derivatives containing natural 2,5-diketopiperazine (DKP) skeleton. Several compounds exhibited distinct HDAC1 inhibitory activities, in particular 2a (IC50 = 405 nM). The selectivity profile for representative 2a indicated that this series of compounds had a preference for HDAC1-3. Additionally, 2a showed the best growth inhibitory activities against K562 and HL-60 tumor cell line with IC50 values of 4.23 and 4.16 µM, respectively. This work may lay the foundation for developing DKP-based HDAC inhibitors as a potential anticancer agent.

Novel 2, 5-diketopiperazine derivatives as potent selective histone deacetylase 6 inhibitors: Rational design, synthesis and antiproliferative activity.

Histone deacetylase 6 (HDAC6) has gained popular attention for its wide participation in various pathological process recently. In this paper, a series of novel derivatives containing 2, 5-diketopiperazine (DKP) skeleton were developed as potent selective HDAC6 inhibitors (sHDAC6is). Most of these compounds exhibited low nanomolar IC50 values toward HDAC6, and the best compound was 21b (IC50 = 0.73 nM) which had 144-10941-fold selectivity over other HDAC isoforms. Western blot assay further validated these compounds to be sHDAC6is. Molecular simulation of 21b was conducted to rationalize the high binding affinity for HDAC6. In the cytotoxicity experiment, 18a, 18b and 18d gave superior or comparable influence on the growth of two multiple myeloma cells U266 and RPMI-8226 compared to ACY-1215. Moreover, the combination of 18a and adriamycin showed synergistic effect against non-small cell lung cancer cell A549. 18a and 18b also demonstrated appropriate drug metabolism in human liver microsome (HLM).

Cyathane diterpenoids and drimane sesquiterpenoids with neurotrophic activity from cultures of the fungus Cyathus africanus.

Five terpenoids, including two new cyathane diterpenoids neocyathin S (1) and neocyathin T (2), together with three drimane sesquiterpenoids, one known 3ß,6ß-dihydroxycinnamolide (3), two new ones 3ß,6α-dihydroxycinnamolide (4) and 2-keto-3ß,6ß-dihydroxycinnamolide (5), were isolated from the cultures of the basidiomycete Cyathus africanus. Their structures were established based on extensive spectroscopic methods including 2D NMR (HSQC, 1H‒1H-COSY, HMBC, ROESY) and HRESIMS experiments. The absolute configurations of two pairs of epimers, 1 and 2 as well as 3 and 4, were determined by ECD quantum chemical calculation. All the five compounds enhanced nerve growth factor (NGF)-mediated neurite outgrowth using rat pheochromocytoma (PC12) cells at concentration 10 µM.

Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by Modulating NGF Signaling in PC12 Cells.

Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous mechanical understanding. In this work, sarcodonin G was chosen as a lead compound to prepare a series of 19- O-benzoyl derivatives by semisynthesis and their neuritogenic activities were evaluated. 6 and 15 (10 µM) were investigated with opposite effects in PC12 cells. 6 exhibited a superior activity to sarcodonin G by promoting NGF-induced neurite outgrowth, while 15 showed an inhibitory effect. Supportingly, 6 and 15 (20 µM) significantly induced and suppressed neurite extension in primary cultured rat cortical neurons, respectively. In mechanism, the two derivatives were revealed to influence NGF-induced neurite outgrowth in PC12 cells through the regulation of PKC-dependent and -independent ERK/CREB signaling as well as the upstream TrkA receptor phosphorylation. Furthermore, a possible pattern of interaction among NGF, 6/15 and TrkA was presented using molecular simulations. It revealed that 6/15 may contribute to the stabilization of the NGF-TrkAd5 complex by establishing several hydrophobic and hydrogen-bond interactions with NGF and TrkA, respectively. Taken together, 6 and 15 modulate PKC-dependent and -independent ERK/CREB signaling pathways possibly by influencing the binding affinity of NGF to the receptor TrkA, and finally regulate neurite outgrowth in PC12 cells.

Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities.

In a previous study, we reported ten new polyoxygenated cyathane diterpenoids, neocyathins A-J, and their anti-neuroinflammatory effects from the liquid culture of the medicinal Basidiomycete Cyathus africanus. In the present study, eight new highly polyoxygenated cyathane diterpenoids, named neocyathins K-R (1-8), were isolated from the solid culture of C. africanus cultivated on cooked rice, together with three known congeners (9-11). The structures and the absolute configurations of the new compounds were elucidated through comprehensive NMR and HRESIMS spectroscopic data, electronic circular dichroism (ECD) data, and chemical conversion. Compounds 1 and 2 represent the first reported naturally occurring compounds with 4,9-seco-cyathane carbon skeleton incorporating an unprecedented medium-sized 9/7 fused ring system, while the 3,4-seco-cyathane derivative (3) was isolated from Cyathus species for the first time. All compounds were evaluated for their neurotrophic and anti-neuroinflammatory activity. All the isolates at 1-25 µM displayed differential nerve growth factor (NGF)-induced neurite outgrowth-promoting activity in PC-12 cells, while one of the compounds, allocyathin B2 (11), inhibited NO production in lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. In addition, molecular docking studies showed that compound 11 generated interactions with the inducible nitric oxide synthase (iNOS) protein.

Hyperelatosides A-E, biphenyl ether glycosides from Hypericum elatoides, with neurotrophic activity.

Five new biphenyl ether glycosides, hyperelatosides A-E (1-5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7-15), were isolated from the aerial parts of Hypericum elatoides. Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed. Except for 3, the new phenolic metabolites exhibited significant neurotrophic activities to enhance nerve growth factor-induced neurite outgrowth in PC12 cells. In addition, the anti-neuroinflammatory and antioxidant activities of compounds 1-15 were preliminarily evaluated in vitro.

Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway.

Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,3-5,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.

Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions.

[3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc)3 mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47µM, and compound 5p exhibted highest activity on HeLa cells with IC50 vaule of 2.32µM. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochemistry studies and cell cycle distribution analysis indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, molecular docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin.

Quantum dots modified with quaternized poly(dimethylaminoethyl methacrylate) for selective recognition and killing of bacteria over mammalian cells.

Copper-free click chemistry has been used to graft quaternized poly(dimethylaminoethyl methacrylate) (QPA) modified with azide to the quantum dots (QDs) derived with dibenzocyclooctynes (DBCO). The success of the quaternary ammonium polymer-modified QDs was confirmed by ultraviolet-visible spectrophotometry (UV-Vis), fluorescence spectroscopy, zeta (ζ) potential, size distribution, and transmission electron microscopy (TEM). The QPA-modified QDs exhibited properties of selective recognition and killing of bacteria. The novelty of this study lies in fact that the synthesis method of the antimicrobial QPA-modified QDs is simple. Moreover, from another standpoint, QPA-modified QDs simultaneously possess abilities of selective recognition and killing of bacteria over mammalian cells, which is very different from the currently designed multifunctional antimicrobial systems composed of complicated systematic compositions.