Copper-catalysed dehydrogenation or lactonization of C(sp3)-H bonds.

Cytochrome P450 enzymes are known to catalyse bimodal oxidation of aliphatic acids via radical intermediates, which partition between pathways of hydroxylation and desaturation1,2. Developing analogous catalytic systems for remote C-H functionalization remains a significant challenge3-5. Here, we report the development of Cu(I)-catalysed bimodal dehydrogenation/lactonization reactions of synthetically common N-methoxyamides through radical abstractions of the γ-aliphatic C-H bonds. The feasibility of switching from dehydrogenation to lactonization is also demonstrated by altering reaction conditions. The use of a readily available amide as both radical precursor and internal oxidant allows for the development of redox-neutral C-H functionalization reactions with methanol as the sole side product. These C-H functionalization reactions using a Cu(I) catalyst with loading as low as 0.5 mol.% is applied to the diversification of a wide range of aliphatic acids including drug molecules and natural products. The exceptional compatibility of this catalytic system with a wide range of oxidatively sensitive functionality demonstrates the unique advantage of using a simple amide substrate as a mild internal oxidant.

Discovery of acetophenone/piperazin-2-one hybrids as selective anti-TNBC cancer agents by causing DNA damage.

Twenty-five acetophenone/piperazin-2-one (APPA) hybrids were designed and synthesized based on key pharmacophores found in anti-breast cancer drugs Neratinib, Palbociclib, and Olaparib. Compound 1j exhibited good in vitro antiproliferative activity (IC50 = 6.50 µM) and high selectivity (SI = 9.2 vs HER2-positive breast cancer cells SKBr3; SI = 7.3 vs normal breast cells MCF-10A) against triple negative breast cancer (TNBC) cells MDA-MB-468. In addition, 1j could selectively cause DNA damage, inducing the accumulation of γH2AX and P53 in MDA-MB-468 cells. It also reduced the phosphorylation level of P38 and the expression of HSP70, which further prevented the repair of DNA damage and caused cells S/G2-arrest leading to MDA-MB-468 cells death.

Environmental Heat Stress Decreases Sperm Motility by Disrupting the Diurnal Rhythms of Rumen Microbes and Metabolites in Hu Rams.

Heat stress (HS) has become a common stressor, owing to the increasing frequency of extreme high-temperature weather triggered by global warming, which has seriously affected the reproductive capacity of important livestock such as sheep. However, little is known about whether HS reduces sperm motility by inducing circadian rhythm disorders in rumen microorganisms and metabolites in sheep. In this study, the year-round reproduction of two-year-old Hu rams was selected, and the samples were collected in May and July 2022 at average environmental temperatures between 18.71 °C and 33.58 °C, respectively. The experiment revealed that the mean temperature-humidity index was 86.34 in July, indicating that Hu rams suffered from HS. Our research revealed that HS significantly decreased sperm motility in Hu rams. Microbiome analysis further revealed that HS reshaped the composition and circadian rhythm of rumen microorganisms, leading to the circadian disruption of microorganisms that drive cortisol and testosterone synthesis. Serum indicators further confirmed that HS significantly increased the concentrations of cortisol during the daytime and decreased the testosterone concentration at the highest body temperature. Untargeted metabolomics analysis revealed that the circadian rhythm of rumen fluid metabolites in the HS group was enriched by the cortisol and steroid synthesis pathways. Moreover, HS downregulated metabolites, such as kaempferol and L-tryptophan in rumen fluid and seminal plasma, which are associated with promotion of spermatogenesis and sperm motility; furthermore, these metabolites were found to be strongly positively correlated with Veillonellaceae_UCG_001. Overall, this study revealed the relationship between the HS-induced circadian rhythm disruption of rumen microorganisms and metabolites and sperm motility decline. Our findings provide a new perspective for further interventions in enhancing sheep sperm motility with regard to the circadian time scale.

Serum antiretinal antibodies and cytokine profiling in autoimmune retinopathy and their association with clinical outcomes.

PURPOSE: Autoimmune retinopathy (AIR) is a group of autoimmune retinal diseases that can cause blindness. The purpose of this study is to investigate the profiles of serum antiretinal antibodies (ARAs) and cytokines and their association with disease diagnosis as well as clinical features in AIR. METHODS: The patients with presumed para (p) and non-paraneoplastic (np) AIR diagnosis, the patients with retinitis pigmentosa and bilateral uveitis as disease controls, and healthy subjects were prospectively enrolled. Western blotting and Luminex multiple cytokine assay/enzyme linked immunosorbent assay were used to determine the presence of serum ARAs and the concentration of cytokines, respectively. Kruskal-Wallis or chi square test was applied to compare the profiles of ARA and cytokines among various groups. The multilevel mixed-effect regression was used to investigate the association of ARA or cytokines with clinical features. RESULTS: No significant difference in the band number and subtypes of serum ARAs was found between AIR patients and their controls. AIR patients had higher concentration of serum IFN-ɤ, CXCL9, or CXCL10 than non-AIR controls. A positive correlation was found between increased number of ARAs and elevated TNF-α in np-AIR patients. Elevated pro-inflammatory cytokines or ARA subtypes (antibody against recoverin and α-enolase) were associated with worse retinal functions or anatomy, including visual acuity, visual field, ERG parameters, and central retinal thickness. CONCLUSIONS: The data of our study demonstrate that detection of serum ARAs has limited value in the diagnosis of AIR. Th1-type cytokines/chemokines or specific ARA subtypes are associated with pathogenesis and disease severity of the AIR.

[Materia medica resources benefits Lancang-Mekong River:a new approach for sub-regional cooperation on traditional medicine].

Lancang-Mekong Cooperation is a new type of subregional cooperation mechanism initiated and built by China and other five countries of the Lancang-Mekong subregion, namely Laos, Myanmar, Thailand, Cambodia, and Vietnam. Countries in the Lancang-Mekong subregion are geographically and culturally connected, and they have nurtured their unique traditional medicine. By combing the history of traditional medicine exchanges between China and other Lancang-Mekong countries and their progress of modern research, this paper summarized the challenges and opportunities of traditional medicine cooperation in the Lancang-Mekong subregion. It has been found that many regional cooperation mechanisms coexist for a long time in the Lancang-Mekong subregion and the medicinal resources are abundant. However, the degree of their development and utilization varies, and modern scientific research is insufficient. Lancang-Mekong Cooperation has provided a strong support for integrating the advantageous resources in Lancang-Mekong subregion countries and making progress together. Focusing on the development and protection of medicinal resources, this paper puts forward a new path of cooperation in the intellectual property rights and characteristic seed resource protection, the compilation of universal herbal pharmacopoeia in various countries, the research and development of public health products, and the construction of traditional herbal industry bases, thus enabling the traditional medicine to better protect the public health and building a human health community.

Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins.

Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and how secreted miRNAs affect vascular permeability remains unclear. Based on deep sequencing and quantitative PCR, we found that higher level of serum miR-103 was associated with higher metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial permeability and transendothelial invasion assays revealed that the conditioned media or exosomes derived from high miR-103-expressing hepatoma cells increased the permeability of endothelial monolayers, but this effect was attenuated if exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if miR-103 within hepatoma or endothelial cells was antagonized. Most importantly, pretreating endothelial monolayers with exosomes that were from stable miR-103-expressing hepatoma cells facilitated the transendothelial invasion of tumor cells, and this role of exosomes was abrogated by inhibiting miR-103 in endothelial cells. Further in vivo analyses disclosed that mice with xenografts of stable miR-103-expressing hepatoma cells exhibited higher vascular permeability in tumor, higher level of exosomal miR-103 and greater number of tumor cells in blood circulation, and increased rates of hepatic and pulmonary metastases, compared to control mice. Mechanism investigations revealed that hepatoma cell-secreted miR-103 could be delivered into endothelial cells via exosomes, and then attenuated the endothelial junction integrity by directly inhibiting the expression of VE-Cadherin (VE-Cad), p120-catenin (p120) and zonula occludens 1. Moreover, miR-103 could also promote tumor cell migration by repressing p120 expression in hepatoma cells. CONCLUSION: Hepatoma cell-secreted exosomal miR-103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR-103 as a potential therapeutic target and a predictive marker for HCC metastasis. (Hepatology 2018).

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters.

We have previously shown that vessels that encapsulated tumour cluster (VETC), a prevalent vascular pattern in hepatocellular carcinoma (HCC), facilitates the entry of the whole tumour cluster into the bloodstream in an invasion-independent manner, and that angiopoietin 2 (Angpt2), the levels of which are increased in HCC cells, is essential for VETC formation. However, the mechanisms underlying VETC formation remains unclear. Herein, we characterized miR-125b and miR-100 as novel VETC suppressors by using human HCC specimens, and cell and animal models. We showed that reduced expression of either miR-125b or miR-100 in human HCC tissues was significantly associated with the presence of VETC, venous invasion of tumour cells, and the occurrence of endothelium-coated microemboli. To confirm the role of miR-125b and miR-100 in VETC formation and HCC metastasis, cell lines with stable miR-125b and miR-100 expression were established by using human VETC-2 cells and mouse Hepa1-6 cells, the hepatoma cells that developed xenografts with VETC patterns. Our results showed that expression of miR-125b or miR-100 in VETC-2 and Hepa1-6 cells dramatically reduced VETC formation in xenografts, and consequently inhibited in vivo metastasis, suggesting that miR-125b and miR-100 may attenuate metastasis by repressing VETC formation. Further investigation revealed that miR-125b directly suppressed the expression of Angpt2 by binding to its 3'-untranslated region, whereas miR-100 reduced the protein level of Angpt2 by targeting mechanistic target of rapamycin (MTOR) and blocking the MTOR-p70S6K signalling pathway. Moreover, the suppressive effect of miR-125b and miR-100 on VETC formation was abrogated by injecting Angpt2-expressing viruses into xenografts. Taken together, our findings imply that miR-125b and miR-100 negatively regulate Angpt2 expression through different mechanisms, in turn inhibit VETC formation, and consequently abrogate the VETC-dependent metastasis of hepatoma cells. This study uncovers new regulatory mechanisms of VETC formation, identifies novel functions of miR-125b and miR-100, and provides new targets for antimetastasis therapy of HCC. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Biomimetic-Functionalized, Tannic Acid-Templated Mesoporous Silica as a New Support for Immobilization of NHase.

Tannic acid-templated mesoporous silica (TAMS) was synthesized using a simple nonsurfactant template method and dopamine-functionalized TAMS (Dop-TAMS), which was prepared via a biomimetic coating, was developed as a new support for immobilization of NHase (NHase@Dop-TAMS). The Dop-TAMS was thoroughly characterized by the transmission electron microscopy (TEM), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), and Fourier transform infrared (FT-IR) and the results showed that the Dop-TAMS possessed sufficiently large pore size and volume for the accommodation of NHase. Studying the thermal stability, storage, shaking stability, and pH stability of the free and immobilized NHase indicated that the catalytic properties of NHase@Dop-TAMS were significantly enhanced. Moreover, the NHase@Dop-TAMS exhibited good reusability. All the results demonstrated that Dop-TAMS could be used as an excellent matrix for the immobilization of NHase.

Identification and characterization of microRNAs in the ovaries of multiple and uniparous goats (Capra hircus) during follicular phase.

BACKGROUND: Superior kidding rate is an important economic trait in production of meat goat, and ovulation rate is the precondition of kidding rate. MicroRNAs (miRNAs) play critical roles in almost all ovarian biological processes, including folliculogenesis, follicle development, follicle atresia, luteal development and regression. To find out the different ovarian activity and follicle recruitment with miRNA-mediated posttranscriptional regulation, the small RNAs expressed pattern in the ovarian tissues of multiple and uniparous Anhui White goats during follicular phase was analyzed using Solexa sequencing data. RESULTS: 1008 miRNAs co-expressed, 309 and 433 miRNAs specifically expressed in the ovaries of multiple and uniparous goats during follicular phase were identified. The 10 most highly expressed miRNAs in the multiple library were also the highest expressed in the uniparous library, and there were no significantly different between each other. The highest specific expressed miRNA in the multiple library was miR-29c, and the one in the uniparous library was miR-6406. 35 novel miRNAs were predicted in total. GO annotation and KEGG Pathway analyses were implemented on target genes of all miRNA in two libraries. RT-PCR was applied to detect the expression level of 5 randomly selected miRNAs in multiple and uniparous hircine ovaries, and the results were consistent with the Solexa sequencing data. CONCLUSIONS: In the present study, the different expression of miRNAs in the ovaries of multiple and uniparous goats during follicular phase were characterized and investigated using deep sequencing technology. The result will help to further understand the role of miRNAs in kidding rate regulation and also may help to identify miRNAs which could be potentially used to increase hircine ovulation rate and kidding rate in the future.

Regulatory role of lncMD1 in goat skeletal muscle satellite cell differentiation via miR-133a-3p and miR-361-3p targeting.

Skeletal muscle satellite cells (SMSCs) are pivotal in skeletal muscle development and are influenced by numerous regulatory factors. This study focuses on the regulatory and functional mechanism roles of lncMD1, a muscle-specific long non-coding RNA, in the proliferation and differentiation of goat SMSCs. Employing in vitro cultured goat SMSCs, this study demonstrated that lncMD1, functions as a decoy for miR-133a-3p and miR-361-3p. This interaction competitively binds these microRNAs to modulate the expression of dynactin subunit 2 (DCTN2) and dynactin subunit 1 (DCTN1), thereby affects SMSCs proliferation and differentiation. These findings enhance the understanding of non-coding RNAs in goat SMSCs growth cycles and offer a theoretical foundation for exploring the molecular processes of goat skeletal muscle myogenic development.

Comparative Proteomic Identification of Ram Sperm before and after In Vitro Capacitation.

Ram sperm undergo a sequence of physiological and biochemical changes collectively termed as capacitation to perform oocyte fertilization. However, the protein changes induced by capacitation remain in need of further exploration. Thus, the present study investigated the comparative proteomic profiling in ram spermatozoa under non-capacitating (NC) and capacitating (CAP) conditions in vitro using a liquid chromatography-tandem mass spectrometry combined with tandem mass tag labeling strategy. As a results, 2050 proteins were identified and quantified; 348 of them were differentially abundant, with 280 of the proteins upregulated and 68 of the proteins downregulated between the CAP and NC spermatozoa, respectively. Functional enrichment analysis indicated that the differentially abundant proteins Prune Exopolyphosphatase 1, Galactose-1-Phosphate Uridylyltransferase, and ATP Citrate Lyase were strictly related to energy production and conversion, and Phosphoglycolate phosphatase, Glucosamine-6-Phosphate Deaminase 1 and 2 were related to metabolism, RNA processing, and vesicular transport pathways. Furthermore, the networks of protein-protein interaction indicated a strong interaction among these differential proteins in annotated pathways such as ubiquitin and transport metabolism. Our findings indicate that capacitation progress might be regulated through different pathways, providing insights into mechanisms involved in ram sperm capacitation and fertility.

Comparison of Clinical and Immunological Features of Para- and Non-Paraneoplastic Autoimmune Retinopathy in Chinese - A Series of 48 Cases.

PURPOSE: To characterize and compare clinical and immunological features of para(p)-autoimmune retinopathy (AIR) and non-para(np)-AIR and to assess the clinical significance of the presence of serum anti-retinal antibodies (ARAs). METHODS: We retrospectively reviewed 48 Chinese patients with p-AIR or np-AIR who took comprehensive ophthalmic examinations and lab tests of the presence of serum ARAs. RESULTS: p-AIR patients differed from np-AIR patients in terms of disease progression, ocular inflammation, findings of OCT, FFA, and presence of ARAs. No significant difference was found in the band number of serum ARAs between AIR patients and healthy controls. The prevalence of antibodies to recoverin and ɑ-enolase in the sera of p-AIR was significantly higher than that of the healthy individuals. CONCLUSION: While having many similar clinical signs, patients with p-AIR or np-AIR nevertheless displayed unique characteristics. Detection of ARAs subtypes, rather than their quantity, may be helpful in evaluating the conditions in the verified instances.

Microbiome-metabolomics analysis of the effects of decreasing dietary crude protein content on goat rumen mictobiota and metabolites.

OBJECTIVE: The objective of this study was to investigate the effects of decreasing dietary crude protein content on rumen fermentation, mictobiota, and metabolites in goats. METHODS: In an 84-day feeding trial, a total of twelve male Anhui white goat kids with initial body weight 15.9±1.13 kg were selected and randomly classified into two groups, feeding a normal crude protein diet (14.8% CP, NCP) or a low crude protein diet (12.0% CP, LCP). At the end of the experimental trial (on day 84), six animals were randomly selected from each group and were slaughtered to collect rumen fluid samples for the analysis of rumen fermentation parameters, microbiome, and metabolome. RESULTS: The concentrations of ammonia-nitrogen, total volatile fatty acid, acetate, and propionate were decreased (p<0.05) in the LCP group in comparison with those in the NCP group. The abundances of genera Prevotella, Campylobacter, Synergistetes, and TG5, which were associated with nitrogen metabolism, were lower (p<0.05) in the LCP group compared with those in the NCP group. The levels of 78 metabolites (74 decreased, 4 increased) in the rumen fluid were altered (p<0.05) by the treatment. Most of the ruminal metabolites that showed decreased levels in the LCP group were substrates for microbial protein synthesis. Metabolic pathway analysis showed that vitamin B6 metabolism was significantly different (p<0.05) in rumen fluid between the two treatments. CONCLUSION: Decreased dietary protein level inhibited rumen fermentation through microbiome and metabolome shifts in goat kids. These results enhance our understanding of ruminal bacteria and metabolites of goat fed a low protein diet.

One-year efficacy of intravitreal conbercept injection for macular oedema secondary to central retinal vein occlusion in Chinese patients.

PURPOSE: To evaluate intravitreal conbercept injection for treatment of macular oedema secondary to central retinal vein occlusion (CRVO) in Chinese patients during 1-year follow-up in the real-world setting. METHODS: Twenty-seven eyes of 27 patients with macular oedema associated with CRVO were retrospectively reviewed. The eyes received monthly intravitreal conbercept injection (0.5 mg in 50 µl) for 3 months. From then on, the patients were followed up every month and received injection pro re nata (PRN) up to 12 months. The primary outcome measurements included changes of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 3 and month 12. Other outcome measurements included proportion of patients gaining ≥15 letters in BCVA at month 3 and 12, the mean number of injections and safety concerns. RESULTS: The mean BCVA gain from baseline was 12.7 ± 7.6 letters at month 3 and 14.8 ± 9.6 letters at month 12. The mean CRT reduction from baseline was 374.5 ± 280.7 µm at month 3 and 428.2 ± 241.3 µm at month 12. The proportion of patients who gained ≥15 letters in BCVA was 45.1% at month 3 and 52.9% at month 12. The mean number of injections was 7.6 ± 1.5. No severe local and systemic complications occurred following injection. CONCLUSIONS: Intravitreal conbercept injection by three monthly loading doses followed by PRN treatment regimen was safe and efficacious for patients with macular oedema secondary to CRVO through 1-year follow-up.

Progress in the basic and clinical research on the Schlemm's canal.

Glaucoma is a leading cause of irreversible blindness in the world. Intraocular pressure (IOP) plays a key role in glaucoma development and progression. Schlemm's canal (SC), an important structure of the anterior chamber angle, regulates the flow of aqueous humor and maintains IOP. Because of its special function of aqueous outflow, the SC has been intensive investigated recently. Several characteristics of SC in anatomy, physiology and pathophysiology have been revealed. Compare to normal, glaucomatous SC cells are more sensitive to substrate stiffness, have higher stiffness and and lower porosity leading to higher outflow resistance. And SC collapse caused by acute IOP increase is partially or totally reversal. With advanced inspection techniques, high-quality images of the SC can be obtained in vivo, which facilitates SC quantitative measurements clinically and allows us to investigate a new therapy paradigm for glaucoma. In this review, we summarize the basic and clinical research that focused on mechanisms of aqueous outflow resistance and SC changes in physiological, pathological, and post-treatment states.

Regulatory Role of the MicroRNA-29b-IL-6 Signaling in the Formation of Vascular Mimicry.

Vascular mimicry (VM) is a critical complement for microcirculation and is implicated in tumor progression. We showed that IL-6 derived from tumor cells and stroma cells promoted tumor cells to form a VM structure, whereas blocking the IL-6 signaling by RNA interference, IL-6-neutralizing antibody, or STAT3 inhibitor suppressed the VM formation of tumor cells. Mechanism investigations revealed that IL-6 stimulated VM formation by activating STAT3, in turn upregulating VE-cadherin expression and MMP2 activity. Further analyses identified a positive association between the activation of IL-6-STAT3 signaling and the formation of the VM structure in human HCC tissues. However, miR-29b repressed the expression of STAT3 and MMP2 by directly binding to the 3' UTRs of their mRNAs. Consistently, both gain- and loss-of-function analyses showed that miR-29b suppressed tumor cells to form tube structures in vitro. The in vivo studies further disclosed that intratumoral injection of the miR-29b-expressing viruses significantly inhibited the IL-6-promoted VM formation in mouse xenografts, and downregulation of miR-29b was correlated with the presence of VM in human HCC tissues. This study elucidates a miR-29b-IL-6 signaling cascade and its role in VM formation, which provide potential targets for cancer therapy.

[Effects of Different Precious Metal Loads of CDPF on Characteristics of VOCs Emissions from a Diesel Bus].

Based on heavy chassis dynamometers, an experimental study was conducted in a diesel bus with proton transfer reaction mass spectrometry (PTR-MS). It investigated the effects of volatile organic compound (VOC) emission characteristics with three different diesel oxidation catalyst (DOC)+catalyzed diesel particulate filter (CDPF) after-treatments for a typical Chinese city bus driving cycle (CCBC). The results reveal that the major compounds from the diesel bus are OVOCs, aromatic hydrocarbons, alkenes, alkanes, nitrogenous organic compounds, and polycyclic aromatic hydrocarbons (PAH), and that the OVOCs account for more than 50%of the total VOCs. With the same precious metal composition and ratio of the proportion in the CDPF catalyst, the emissions of VOCs decrease with an increase in precious metal load. The emission reduction rates of the VOCs are 36.2%, 40.1%, and 41.4%, respectively, when the precious metal loads are 15 g·ft-3 (type A after-treatment device), 25 g·ft-3 (type B), and 35 g·ft-3 (type C). The average emission rates of alkanes for the three kinds of DOC+CDPF after-treatments are all over 59% for the entire CCBC cycle. The type C after-treatment device can reduce the alkane emissions by 70.2%, with a slight advantage for the OVOC reduction compared with type A and type B devices. For unsaturated hydrocarbons, including aromatic hydrocarbons, alkenes, and PAHs, the after-treatment devices have a catalytic effect, but there is no significant difference between them. The emissions of nitrogenous organic compounds are greatly decreased, by 50.5%, with the type A after-treatment, but the reduction rate decreases with an increase in precious metal load. In addition, OVOCs, aromatic hydrocarbons, and alkenes are the most important contributors to ozone formation. The adoption of DOC+CDPF reduces the emissions of VOCs and, therefore, the ozone formation potential. Taking into account the emission reduction rates and costs of the three different after-treatments and for weighting coefficients of 0.8 and 0.2, respectively, the type B after-treatment is the optimal solution.

The effects of pulsed low-intensity ultrasound on chondrocyte viability, proliferation, gene expression and matrix production.

This study was designed to examine the effects of pulsed low-intensity ultrasound (PLIUS) on chondrocyte viability, proliferation, matrix production and gene expression. Chondrocytes were isolated from the distal part of the sternum of 16-day-old chick embryos and cultured in alginate beads. PLIUS at 2 mW/cm(2) (group PLIUS(2)) and 30 mW/cm(2) (group PLIUS(30)) was applied to chondrocytes for a single 20-min treatment. A control group was treated without PLIUS. The viability of chondrocytes was not affected by exposure to PLIUS. PLIUS influenced chondrocyte proliferation in an intensity-dependent manner. By day 7 after application of PLIUS, the gene expression and synthesis of aggrecan was the same as in the controls. At this same time point, the expression and synthesis of type II collagen was not different between the controls and PLIUS(30), but was increased in PLIUS(2). PLIUS was shown to inhibit the expression of type X collagen. This inhibition of chondrocyte hypertrophy may prove to be significant in the management of cartilage degeneration.

Integration of RAFT polymerization and click chemistry to fabricate PAMPS modified macroporous polypropylene membrane for protein fouling mitigation.

A copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) grafting-to method was used to tether alkyne-terminated poly(2-acrylamido-2-methyl propane sulfonic acid) (alkyne-PAMPS) to the azide functionalized macroporous polypropylene membrane (MPPM-N3). Alkyne-PAMPS was synthesized by the reversible addition-fragmentation chain transfer polymerization (RAFT) of AMPS with an alkyne-terminated trithiocarbonate served as a chain transfer agent. The combination of RAFT polymerization with click chemistry to graft polymer to the surface of polypropylene membrane produced relatively high grafting density and controllable grafting chain length. The structure and composition of the modified and unmodified MPPM surfaces were analyzed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR/FT-IR), X-ray photoelectron spectroscopy (XPS); field emission scanning electron microscopy (FE-SEM) was employed to observe the morphological changes on the membrane surface. The permeation performances were tested by the filtration of protein dispersion. The experimental results show that with the grafting degree going up, the relative flux reduction decreases, while the relative flux recovery ratio increases, and the protein fouling is obviously mitigated by tethering PAMPS to the membrane surface. The modified membranes can be potentially applied for fouling reduction during the filtration of proteins.