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1.
Food Chem ; 338: 128025, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32927200

RESUMO

Short-chain fatty acid esters are important flavor chemicals in Chinese traditional fermented Baijiu. Monascus purpureus was recognized as an important microorganism contributing to ester synthesis. However, the molecular basis for ester synthesis was still lacking. The present work combined genome sequencing, transcriptome sequencing, gene library construction, and enzyme engineering to discover a novel catalyst from M. purpureus (isolated from Baijiu fermentation starter). Enzyme LIP05, belonging to the α/ß hydrolase family, was identified to synthesize short-chain fatty acid esters under aqueous phase. After deleting the lid domain of LIP05, the synthesis of ethyl pentanoate, ethyl hexanoate, ethyl octanoate, or ethyl decanoate was achieved. Ethyl octanoate with the highest conversion ratio of 93.7% was obtained with the assistance of ultrasound. The study reveals the molecular basis for synthesizing short-chain fatty acid esters by M. purpureus and will promote the application of the species or the enzyme in food industry.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32920203

RESUMO

The vitellogenin receptor (Vgr), which is specific for vitellogenin (Vtg), recognises and transports Vtg into the ovaries. Accumulating evidence suggests that Vtg also performs an immune defence function and plays critical roles in innate immunity in oviparous animals. However, whether Vgr is involved in innate immunity in the Chinese mitten crab (Eriocheir sinensis) is unknown. In this study, we obtained a 3009 nucleotide partial cDNA of the E. sinensis vitellogenin receptor gene (Es-vgr) encoding an open reading frame of 1003 amino acid residues. Bioinformatics analysis showed that the domains of Es-vgr were conserved during evolution. Quantitative real-time PCR and western blotting revealed that the highest Es-vgr expression levels occurred in the ovary, and expression was specific. Comparison of the expression levels of Es-vgr and the Vtg gene (Es-vtg1) at different ovary developmental stages suggested that there may be some regulatory relationship between them. Bacterial challenge induced high-level expression of antimicrobial peptide genes and reduced Es-vgr expression in ovaries, resulting in massive accumulation of Vtg in the hemolymph. The survival rate of crabs increased significantly after injection with recombinant Es-vtg1 protein following bacterial infection. Collectively, these results demonstrate that Es-vgr plays critical roles in antimicrobial function by regulating the accumulation of Vtg in the hemolymph.

3.
Nanotechnology ; 31(48): 485202, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32931468

RESUMO

Full static x-ray computed tomography (CT) technology has enabled higher precision and resolution imaging and has been applied in many applications such as diagnostic medical imaging, industrial inspection and security screening. In this technique, the x-ray source section is mainly composed of a thermionic cathode and electron beam scanning system. However, they have several shortcomings such as limited scanning angle, long response time and large volume. Distributed and programmable cold cathode (i.e. carbon nanotubes, ZnO nanowires (NWs)) field-emission x-ray sources are expected to solve these problems. However, there have been several long-standing challenges to the application of such cold field emitters for x-ray sources, such as the short lifetime and rigorous fabrication process, which have fundamentally prevented their widespread use. Here, we propose and demonstrate a cold field-emission x-ray source based on a graphene oxide (GO)-coated cuprous sulfide nanowire (Cu2S NW/GO) cathode. The proposed Cu2S NW/GO x-ray source provides stable emission (>18 h at a direct voltage of 2600 V) and has a low threshold (4.5 MV m-1 for obtaining a current density of 1 µA cm-2), benefiting from the demonstrated key features such as in situ epitaxy growth of Cu2S NWs on Cu, nanometer-scale sharp protrusions within GO and charge transfer between the Cu2S NWs and GO layer. Our research provides a simple and robust method to obtain a high-performance cold field emitter, leading to great potential for the next generation of x-ray source and CT.

4.
Chem Biol Interact ; : 109246, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32877639

RESUMO

Colorectal cancer (CRC) represents one of the commonest malignancies around the world. PP9, a natural steroidal saponin, was firstly isolated from the rhizomes of Paris polyphylla var. latifolia. However, the therapeutic effects of PP9 on CRC and the underlying molecular mechanism remain undefined. Here, we demonstrated that treatment with PP9 time- and dose-dependently inhibited HT-29 and HCT116 cells without significantly inhibiting normal NCM460 cells. Furthermore, our results indicated that PP9 effectively induced G2/M phase arrest by upregulating p21 and suppressing cdc25C, Cyclin B1 and cdc2. Meanwhile, PP9 upregulated cleaved Caspase 3, cleaved Caspase 9 and cleaved PARP and Bax, while downregulating Bcl-2 to stimulate cell apoptosis. Mechanistically, PP9-suppressed PI3K/Akt/GSK3ß signaling, while the PI3K inhibitor LY294002 augmented PP9-mediated apoptosis, G2/M arrest and effects on PI3K/Akt/GSK3ß related proteins. Finally, we showed that PP9 (10 mg/kg) significantly reduced tumor growth in nude mouse CRC xenografts, more potently than 5-Fu (20 mg/kg). Jointly, these data firstly demonstrated that PP9 promotes G2/M arrest and apoptotic death in CRC cells through PI3K/Akt/GSK3ß signaling suppression, suggesting that PP9 could be considered a new and promising candidate for CRC therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32878999

RESUMO

Trafficking of toll-like receptor 3 (TLR3) from the endoplasmic reticulum (ER) to endolysosomes and its subsequent proteolytic cleavage are required for it to sense viral double-stranded RNA (dsRNA) and trigger antiviral response, yet the underlying mechanisms remain enigmatic. We show that the E3 ubiquitin ligase TRIM3 is mainly located in the Golgi apparatus and transported to the early endosomes upon stimulation with the dsRNA analog poly(I:C). TRIM3 mediates K63-linked polyubiquitination of TLR3 at K831, which is enhanced following poly(I:C) stimulation. The polyubiquitinated TLR3 is recognized and sorted by the ESCRT (endosomal sorting complex required for transport) complexes to endolysosomes. Deficiency of TRIM3 impairs TLR3 trafficking from the Golgi apparatus to endosomes and its subsequent activation. Trim3 -/- cells and mice express lower levels of antiviral genes and show lower levels of inflammatory response following poly(I:C) but not lipopolysaccharide (LPS) stimulation. These findings suggest that TRIM3-mediated polyubiquitination of TLR3 represents a feedback-positive regulatory mechanism for TLR3-mediated innate immune and inflammatory responses.

6.
Fish Shellfish Immunol ; 106: 866-875, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32889097

RESUMO

The innate immune response is an important line of defense against invading pathogens in invertebrates. Signaling pathways, including the IMD pathway, play critical roles in the production of antimicrobial peptides (AMPs), which induce the transcription of immune effectors that protect against bacterial invasion. In the present study, the cDNA of IMD from Eriocheir sinensis was cloned (designated EsIMD) and shown to be significantly upregulated following Gram-positive and Gram-negative bacterial infection. In vivo and in vitro studies collectively suggested that both the Gram-negative bacterium Vibrio parahemolyticus and the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis elicit the translocation of Relish. Moreover, EsIMD positively regulated EsRelish translocation from the cytoplasm to the nucleus following stimulation with both Gram-positive and Gram-negative bacteria. EsRelish knockdown in hemocytes significantly suppressed AMPs' expression. Furthermore, both Lys-type and DAP-type peptidoglycan-containing bacteria activated the IMD pathway and elicited antibacterial responses in crab. Conclusively, these findings demonstrate that both Gram-positive and Gram-negative bacteria activate IMD signaling, via a mechanism that is distinct with that by which Gram-negative bacteria activate IMD signaling in Drosophila. These findings might pave the way for a better understanding of the innate immune system and the fundamental network of the IMD signaling pathway in crustacean.

7.
Mol Med Rep ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32901838

RESUMO

Non­small cell lung cancer (NSCLC) is a leading subtype of lung cancer, with high mortality rates. Recently, long non­coding RNAs (lncRNAs) have been associated with NSCLC. The present study aimed to examine the role of the TP73 antisense RNA 1 (TP73­AS1) lncRNA in NSCLC. TP73­AS1 and microRNA(miR)­34a­5p expression levels were measured using reverse transcription­quantitative PCR (RT­qPCR) and chromogenic in situ hybridization (CISH). Cell proliferation, apoptosis, migration and invasion was determined using Cell Counting Kit­8 (CCK­8), flow cytometry, Transwell and Matrigel assays, respectively. The median inhibitory concentration (IC50) value of cisplatin (cis­diamminedichloroplatinum; DDP) was assessed using a CCK­8 assay. The interaction between miR­34a­5p and TP73­AS1 or tripartite motif­containing 29 (TRIM29) was predicted using microRNA.org and Starbase, then verified using a dual­luciferase reporter assay. The expression of TRIM29 was quantified at the mRNA and protein level using RT­qPCR and western blot analysis, respectively. TP73­AS1 was significantly upregulated, while miR­34a­5p was downregulated in NSCLC tissues and cells. Functionally, TP73­AS1 knockdown inhibited proliferation, migration, invasion and DDP resistance, whilst inducing apoptosis in NSCLC cells. miR­34a­5p was identified as a target for TP73­AS1, and its inhibition reversed the effects of TP73­AS1 knockdown on NSCLC cells. In addition, TRIM29 was targeted by miR­34a­5p, and its overexpression reversed the effects of miR­34a­5p. Moreover, TP73­AS1 acted as a molecular sponge for miR­34a­5p, increasing the expression of TRIM29. In conclusion, TP73­AS1 contributed to proliferation, migration and DDP resistance but inhibited apoptosis of NSCLC cells by upregulating TRIM29 and sponging miR­34a­5p.

8.
Phys Rev Lett ; 125(8): 086803, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32909796

RESUMO

Electrons commonly couple through Fröhlich interactions with longitudinal optical phonons to form polarons. However, trions possess a finite angular momentum and should therefore couple instead to rotational optical phonons. This creates a polaronic trion whose binding energy is determined by the crystallographic orientation of the lattice. Here, we demonstrate theoretically within the Fröhlich approach and experimentally by photoluminescence emission that the bare trion binding energy (20 meV) is significantly enhanced by the phonons at the interface between the two-dimensional semiconductor MoS_{2} and the bulk transition metal oxide SrTiO_{3}. The low-temperature binding energy changes from 60 meV in [001]-oriented substrates to 90 meV for [111] orientation, as a result of the counterintuitive interplay between the rotational axis of the MoS_{2} trion and that of the SrTiO_{3} phonon mode.

9.
Phys Chem Chem Phys ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32915174

RESUMO

Multichromophoric systems with efficient photoinduced excited-state processes are important for the conversion of solar energy in artificial photosynthesis. However, a low molecular absorption coefficient of these multichromophoric systems in the near-infrared region limits their power conversion efficiency in organic solar cells. It is critical to design molecules with a broad absorption range in the whole spectral region, to better harvest solar energy, and to reveal their important multiple-step photophysical processes for the design of organic solar cells. Here, we investigate a novel compound having three chromophores, namely two near-by N,N'-bis(1-pentyl)hexyl-3,4,9,10-perylenebiscarboximide (PDI) units linked to a zinc porphyrin core side by side (in the form of PDI-ZnPor-PDI), which absorbs solar energy ranging from the ultraviolet (UV) to near-infrared regions. The photophysical behavior of PDI-ZnPor-PDI in both film and solution forms, has been investigated using steady-state and transient spectroscopy measurements. Charge-transfer species and triplet excited-state species are observed, the excited-state evolutions of which are monitored using molecular vibrations as probes. These observations support the idea that PDI-ZnPor-PDI on photoexcitation generates the radical anion and triplet species of the PDI unit (PDI˙- and 3PDI*). Our results demonstrate the effect of solid film state on the photophysical properties in such multichromophoric system, and are valuable for guiding the design and utilization of novel near-infrared electron donors or acceptors for use in organic solar cells.

10.
BMC Musculoskelet Disord ; 21(1): 606, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912166

RESUMO

BACKGROUND: Patients with continuous multi-vertebral lumbar spine tuberculosis (CMLSTB) were subjected to single posterior debridement, interbody fusion, and fixation to explore their clinical outcomes. METHODS: Sixty-seven CMLSTB patients who underwent single posterior debridement interbody fusion and fixation between January 2008 to December 2017 were studied. The operation time, blood loss, perioperative complication rate, cure rate, Visual Analog Scale (VAS), Oswetry disability index (ODI), Japanese Orthopedic Association (JOA), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb's angle and time of interbody fusion were analyzed to understand their therapeutic effects on CMLSTB patients. RESULTS: The patients were followed up for 20-48 months, with a mean of 24.3 months. The mean operation time was 215.5 min (range, 120-280 min), whereas 818.0 ml of blood was lost (range, 400-1500 ml) with a perioperative complication rate of 6.0% and a cure rate of 95.5%. During the last phase of follow-up, the mean preoperative VAS score (5.7) and ODI (72.0%) decreased significantly to 1.4 (t = 31.4, P<0.01) and 8.4% (t = 48.4, P<0.01), respectively. Alternatively, the mean preoperative ESR and CRP (74.7 mm /h and 69.3 mg/L, respectively) decreased to average values (tESR = 39.7, PESR<0.001; tCRP = 50.2, PCRP<0.001), while the JOA score (13.9) significantly increased to 23.0 (t = - 11.6, P<0.01). The preoperative kyphotic Cobb's angle (20.5°) decreased to 4.8° after the operation (t = 14.0, P<0.01); however, the kyphotic correction remained intact at the time of follow-up (t = - 0.476, P = 0.635). Furthermore, the mean of interbody fusion time was identified to be 8.8 months (range, 6-16 months). CONCLUSION: Single posterior debridement, interbody fusion, and fixation may be one of the surgical choices for the treatment of CMLSTB patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32804478

RESUMO

Metal nanofibers with excellent electrical conductivity and superior mechanical flexibility have great potentials for fabrication of lightweight, flexible, and high-performance electromagnetic interference (EMI) shielding architectures. The weak interactions and large contact resistance among the wires, however, hinder their assembly into robust and high-performance EMI shielding monoliths. In this work, we used low fractions of polymers to assist the construction of lightweight, flexible, and highly conductive silver nanowire (AgNW) cellular monoliths with significantly enhanced mechanical strength and EMI shielding effectiveness (SE). The normalized surface specific SE of our AgNW-based cellular monoliths can reach up to 20522 dB·cm2/g, outracing that of most shielding materials ever reported. Moreover, this robust conductive framework enabled the successful fabrication of hydrophobic, ultraflexible, and highly stretchable aerogel/polymer composites with outstanding EMI SE even at an extremely low AgNW content. Thus, this work demonstrated a facile and efficient strategy for assembling metal nanofiber-based functional high-performance EMI shielding architectures.

12.
J Ovarian Res ; 13(1): 90, 2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32772928

RESUMO

BACKGROUND: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. RESULTS: Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3'UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. CONCLUSIONS: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.

13.
Sensors (Basel) ; 20(16)2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32796498

RESUMO

With the widely used monthly gravity models, it is hard to determine the sub-monthly variations. Thanks to the high temporal resolution, a daily ITSG-Grace2018 gravity model is employed to derive the vertical deformation of the China region in 1.0° × 1.0° grids. The standard deviations of residuals between the daily and monthly averaged displacement range from 1.0 to 3.5 mm, reaching half of the median residuals, which indicates that a higher temporal resolution gravity model is quite necessary for the analysis of crustal displacement. For the signal analysis, traditional least square (LS) is limited in its analysis of signals with constant amplitude. However, geophysical signals in a geodetic time series usually fluctuate over long periods, and missing data happen. In this study, the data adaptive approach called enhanced harmonic analysis (EHA), which is based on an Independent Point (IP) scheme, is introduced to deal with these issues. To demonstrate the time-varying signals, the relative differences between EHA and LS are calculated. It illustrates that the median percentage of epochs at grids with a relative difference larger than 10% is 69.7% and the proportions for the ranges of 30%, 50%, and 70% are about 30.1%, 18.4%, and 13.0%, respectively. The obvious discrepancy suggests the advantage of EHA over LS in obtaining time-varying signals. Moreover, the spatial distribution of the discrepancy also demonstrates the regional characteristics, suggesting that the assumption of constant amplitude is not appropriate in specific regions. To further validate the effectiveness of EHA, the comprehensive analysis on the different noise types, number of IPs, missing data, and simultaneous signals are carried out. Specifically, EHA can deal with series containing white or color noise, although the stochastic model for the color noise should be modified. The signals are slightly different when selecting different numbers of IPs within a range, which could be accepted during analysis. Without interpolation, EHA performs well even with continuously missing data, which is regarded as its feature. Meanwhile, not only a single signal but also simultaneous signals can be effectively identified by EHA.

14.
J Alzheimers Dis ; 77(1): 85-98, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32741808

RESUMO

BACKGROUND: Long noncoding RNAs have been proven to play an important role in the progression of Alzheimer's disease (AD). However, the function of small nucleolar RNA host gene 1 (SNHG1) in AD progression remains to be studied. OBJECTIVE: To explore the role of SNHG1 in AD progression and clarify its potential mechanism. METHODS: Amyloid ß-protein (Aß) was used to construct an AD cell model in vitro. The expression levels of SNHG1 and miR-361-3p were determined by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit 8 assay and flow cytometry. The levels of apoptosis-related proteins and zinc finger gene 217 (ZNF217) protein were evaluated by western blot analysis. Additionally, the contents of inflammatory cytokines and oxidative stress markers were tested by enzyme-linked immunosorbent assay. Furthermore, dual-luciferase reporter and RNA immunoprecipitation assays were used to verify the interaction between miR-361-3p and SNHG1 or ZNF217. RESULTS: Aß could induce cell injury, while resveratrol could reverse this effect. SNHG1 expression was positively regulated by Aß and negatively regulated by resveratrol. SNHG1 knockdown could reverse the promotion effect of Aß on cell injury. Moreover, SNHG1 sponged miR-361-3p, and miR-361-3p targeted ZNF217. Additionally, miR-361-3p overexpression reversed the promotion effect of SNHG1 overexpression on cell injury, and ZNF217 silencing also reversed the promotion effect of miR-361-3p inhibitor on cell injury. CONCLUSION: SNHG1 promoted cell injury by regulating the miR-361-3p/ZNF217 axis, which might provide a theoretical basis for molecular therapy of AD.

15.
Chem Commun (Camb) ; 56(72): 10394-10408, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32797138

RESUMO

Conjugated polymers consisting of electron-rich and electron-deficient units as alternative structures have played important roles in the field of organic solar cells (OSCs). A thieno[3,4-c]pyrrole-4,6-dione (TPD) unit as an electron-deficient unit has been used to construct conjugated polymers for application in fullerene and non-fullerene based OSCs. TPD-based monomers can be simply prepared and TPD-polymers can be synthesized via environmentally friendly direct (hetero)arylation polymerization, providing a possibility for large quantity preparation. TPD-polymers usually have deep frontier energy levels, wide band gaps with absorption onset around 700 nm and good charge transport properties, showing the advantages of high open-circuit voltage, high fill-factor and excellent spectral matching with a small band gap non-fullerene acceptor. From the material design and synthesis and their optoelectrical properties, TPD-polymers have great potential applications in OSCs toward large-area devices. In this review, we provide an overview of TPD-polymers for OSCs in the last ten years, including the design and synthesis of TPD-polymers, and their application in fullerene and non-fullerene OSCs. We will also provide some perspective about the research of TPD-polymers that meet the requirement of OSCs. We hope that our universal summary can stimulate the study of TPD-polymers in the future, especially toward high performance, low cost and stable OSCs.

16.
Diagn Cytopathol ; 2020 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-32827355

RESUMO

BACKGROUND: The accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to the rarity of tumor and variable cytologic appearance. The Asian experience with diagnosing MTC by fine-needle aspiration (FNA) was scarcely reported. METHODS: Cases of MTC with available FNA slides were enrolled from 13 hospitals representing 8 Asia-Pacific countries. Clinicopathological information, including sample preparation technique, staining method, original cytologic diagnosis and review diagnosis were collected. RESULTS: Of a total of 145 MTC cases retrospectively recruited, 99 (68.3%) were initially interpreted as MTC/suspicious for MTC (S-MTC). The distribution of original FNA diagnostic categories was not associated with the staining method or sample preparation technique. The staining methods used were Papanicolaou, hematoxylin-eosin and Romanowsky stains. Liquid-based cytology (LBC) was used only in three countries. After reviewing all cases, the diagnostic rate of MTC/S-MTC increased to 91.7% (133/145). Cases with initially unrecognized MTC had either marked pleomorphism or cytology mimicking papillary carcinoma or follicular neoplasm. Although LBC provided certain benefits, there was no significant difference in diagnostic accuracy between conventional smear and LBC. Immunocytochemistry was available in 38 cases (26.2%), all of which were correctly recognized as MTC. CONCLUSION: Our report summarizes how MTC is handled in contemporary Asian thyroid FNA practice. Although the detection rate of MTC by cytology alone is less satisfactory, integration with ancillary tests could achieve an excellent performance. The recognition of constitutive cytomorphologic features is needed for each cytopreparatory method, which may result in a lower threshold to initiate further workup for MTC.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32815586

RESUMO

In this work, a record power conversion efficiency of 8.40% was obtained in single-component organic solar cells (SCOSCs) based on double-cable conjugated polymers. This is realized based on the finding that exciton separation plays the same important role as charge transport in SCOSCs. Herein, we designed two double-cable conjugated polymers with almost the identical conjugated backbones and electron-withdrawing side units, but the extra chlorine (Cl) atoms had different positions on the conjugated backbones. We found that, when Cl atoms were positioned at the main chains, the polymer formed the twist backbones, enabling better miscibility with the naphthalene diimide side units. This could improve the interface contact between conjugated backbones and side units, resulting in efficient conversion of excitons into free charges. These observations were confirmed by systematical studies via several advanced measurements. These findings reveal the importance of charge generation process in SCOSCs and also suggest a strategy to improve this process, that is, controlling the miscibility between conjugated backbones and aromatic side units in double-cable conjugated polymers.

18.
Adv Ther ; 37(10): 4233-4248, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32770529

RESUMO

INTRODUCTION: Although various therapies are available for the treatment of metastatic colorectal cancer (mCRC), there is lack of head-to-head evidence. Recent studies have demonstrated the efficacy of chemotherapy in combination with different biological agents including regorafenib in second-line therapy in patients with mCRC. We conducted a network meta-analysis (NMA) to estimate the relative efficacy and safety of regorafenib in combination with chemotherapy compared to other biological agents with chemotherapy combinations. METHODS: A literature search was conducted in PubMed, Embase, and Cochrane databases to identify all randomized controlled trials (RCTs) evaluating the efficacy and safety of bevacizumab, regorafenib, panitumumab, cetuximab, ramucirumab, conatumumab, ganitumab, and aflibercept in combination with chemotherapy against chemotherapy alone as second-line setting from inception to 7 February 2019 in patients with mCRC. The survival outcomes were analyzed by the frequentist statistical approach (R software, netmeta package) while the level of individual treatment arms was assessed using the Bayesian method (R software, gemtc package). RESULTS: We identified 12 articles involving eight RCTs studies analyzing 6805 patients. The studies compared bevacizumab (3), regorafenib (1), panitumumab (2), cetuximab (3), ramucirumab (1), conatumumab (1), ganitumab (1), and aflibercept (1) against chemotherapy alone as comparator. The progression-free survival (PFS) revealed that regorafenib performed better than aflibercept (HR 0.9631, 95% CI 0.6785-1.367), ganitumab (HR 0.7228, 95% CI 0.3985-1.3109), panitumumab (HR 0.9653, 95% CI 0.6781-1.3742), and ramucirumab (HR 0.9206, 95% CI 0.6504-1.303). Regorafenib performed better than bevacizumab (OR 0.797, 95% CI 0.328-1.88) in terms of tumor response. Safety analysis showed that regorafenib performed better in reducing grade ≥ 3 adverse events (AE) than cetuximab and conatumumab, neutropenia than conatumumab, and fatigue than cetuximab. CONCLUSIONS: Regorafenib combined with chemotherapy might be a potential alternative to conventional therapeutic options in second-line treatment of patients with metastatic colorectal cancer and could be considered as the best option for treating patients with KRAS and BRAF mutated mCRC. However future RCTs are needed to confirm these results.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32683507

RESUMO

Recently, mRNA-based therapeutics have been greatly boosted since the development of novel technologies of both mRNA synthesis and delivery system. Promising results were showed in both preclinical and clinical studies in the field of cancer vaccine, tumor immunotherapy, infectious disease prevention and protein replacement therapy. Recent advancements in clinical trials also encouraged scientists to attempt new applications of mRNA therapy such as gene editing and cell programming. These studies bring mRNA therapeutics closer to real-world application. Herein, we provide an overview of recent advances in mRNA-based therapeutics.

20.
Adv Healthc Mater ; : e2000092, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32729238

RESUMO

Colloidal surface engineering is of particular importance to impart modular functionalities to the colloidal systems. Here, a layer of Mn/Ni layered hydroxides (Mn/Ni(OH)x LDHs) can be successfully coated on various colloidal particles, such as silica spheres, silica rods, ferrite nanocrystal supraparticles, as well as FeOOH nanorods. Such layered hydroxides have intrinsic oxidase-mimetic activities, as demonstrated by catalytic oxidation of tetramethyl benzidine in the presence of oxygen. Furthermore, Mn/Ni(OH)x LDHs structure seems to capture bacteria (both Gram positive and Gram negative) and exhibit antibacterial properties in vitro. Moreover, local delivery of Mn/Ni-LDH structure fights against infection and reverses delayed wound healing procedures in mice models. Importantly, such hierarchical structures may have strong adhesive properties to the bacteria, which may maximize the contact between Mn/Ni(OH)x LDHs and the bacteria's surface. Overall, the present versatile colloidal surface engineering strategy will bring new insights in the field of antibiotics for its high efficiency toward antibacterial activity.

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