Polymeric drug delivery systems have been achieved great development in the last two decades. Polymeric drug delivery has defined as a formulation or a device that enables the introduction of a ...therapeutic substance into the body. Biodegradable and bio-reducible polymers make the magic possible choice for lot of new drug delivery systems. The future prospects of the research for practical applications has required for the development in the field.
Natural polymers such as arginine, chitosan, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid have been treated for polymeric drug delivery systems. Synthetic polymers such as poly (2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide)s, poly(ethylenimine)s, dendritic polymers, biodegradable and bio-absorbable polymers have been also discussed for polymeric drug delivery. Targeting polymeric drug delivery, biomimetic and bio-related polymeric systems, and drug-free macromolecular therapeutics have also treated for polymeric drug delivery. In polymeric gene delivery systems, virial vectors and non-virial vectors for gene delivery have briefly analyzed. The systems of non-virial vectors for gene delivery are polyethylenimine derivatives, polyethylenimine copolymers, and polyethylenimine conjugated bio-reducible polymers, and the systems of virial vectors are DNA conjugates and RNA conjugates for gene delivery.
The development of polymeric drug delivery systems that have based on natural and synthetic polymers are rapidly emerging to pharmaceutical fields. The fruitful progresses have made in the application of biocompatible and bio-related copolymers and dendrimers to cancer treatment, including their use as delivery systems for potent anticancer drugs. Combining perspectives from the synthetic and biological fields will provide a new paradigm for the design of polymeric drug and gene delivery systems.
Immunotoxins (ITs) are attractive anticancer modalities aimed at cancer-specific delivery of highly potent cytotoxic protein toxins. An IT consists of a targeting domain (an antibody, cytokine, or ...another cell-binding protein) chemically conjugated or recombinantly fused to a highly cytotoxic payload (a bacterial and plant toxin or human cytotoxic protein). The mode of action of ITs is killing designated cancer cells through the effector function of toxins in the cytosol after cellular internalization via the targeted cell-specific receptor-mediated endocytosis. Although numerous ITs of diverse structures have been tested in the past decades, only 3 ITs-denileukin diftitox, tagraxofusp, and moxetumomab pasudotox-have been clinically approved for treating hematological cancers. No ITs against solid tumors have been approved for clinical use. In this review, we discuss critical research and development issues associated with ITs that limit their clinical success as well as strategies to overcome these obstacles. The issues include off-target and on-target toxicities, immunogenicity, human cytotoxic proteins, antigen target selection, cytosolic delivery efficacy, solid-tumor targeting, and developability. To realize the therapeutic promise of ITs, novel strategies for safe and effective cytosolic delivery into designated tumors, including solid tumors, are urgently needed.
Semiconducting ink based on 2D single‐crystal flakes with dangling‐bond‐free surfaces enables the implementation of high‐performance devices on form‐free substrates by cost‐effective and scalable ...printing processes. However, the lack of solution‐processed p‐type 2D semiconducting inks with high mobility is an obstacle to the development of complementary integrated circuits. Here, a versatile strategy of doping with Br2 is reported to enhance the hole mobility by orders of magnitude for p‐type transistors with 2D layered materials. Br2‐doped WSe2 transistors show a field‐effect hole mobility of more than 27 cm2 V−1 s−1, and a high on/off current ratio of ≈107, and exhibits excellent operational stability during the on‐off switching, cycling, and bias stressing testing. Moreover, complementary inverters composed of patterned p‐type WSe2 and n‐type MoS2 layered films are demonstrated with an ultra‐high gain of 1280 under a driving voltage (VDD) of 7 V. This work unveils the high potential of solution‐processed 2D semiconductors with low‐temperature processability for flexible devices and monolithic circuitry.
Solution‐processed high‐performance p‐type WSe2 thin‐film transistor is successfully fabricated by Br2‐doping with a field‐effect hole mobility of more than 27 cm2 V−1 s−1, and a high on/off current ratio of ≈107. The resulting complementary inverters with patterned p‐type WSe2 and n‐type MoS2 layered films reaches an ultra‐high gain of 1280 under a driving voltage (VDD) of 7 V.
Sex Differences in Gut Microbiota Kim, Yong Sung; Unno, Tatsuya; Kim, Byung Yong ...
The World Journal of Men's Health,
01/2020, Volume:
38, Issue:
1
Journal Article, Book Review
Peer reviewed
Open access
Humans carry numerous symbiotic microorganisms in their body, most of which are present in the gut. Although recent technological advances have produced extensive research data on gut microbiota, ...there are various confounding factors (
, diet, race, medications) to consider. Sex is one of the important variables affecting the gut microbiota, but the association has not yet been sufficiently investigated. Although the results are inconsistent, several animal and human studies have shown sex differences in gut microbiota. Herein, we review these studies to discuss the sex-dependent differences as well as the possible mechanisms involved.
Semiconductors with a moderate bandgap have enabled modern electronic device technology, and the current scaling trends down to nanometer scale have introduced two-dimensional (2D) semiconductors. ...The bandgap of a semiconductor has been an intrinsic property independent of the environments and determined fundamental semiconductor device characteristics. In contrast to bulk semiconductors, we demonstrate that an atomically thin two-dimensional semiconductor has a bandgap with strong dependence on dielectric environments. Specifically, monolayer MoS2 bandgap is shown to change from 2.8 eV to 1.9 eV by dielectric environment. Utilizing the bandgap modulation property, a tunable bandgap transistor, which can be in general made of a two-dimensional semiconductor, is proposed.
Electron‐injecting interlayers (ILs) which are stable in air, inject electrons efficiently, block holes, and block quenching of excitons, are very important to realize efficient inverted polymer ...light‐emitting diodes (IPLEDs). Two air‐stable polymer electron‐injecting interlayers (ILs), branched polyethyleneimine (PEI) and polyethyleneimine ethoxylated (PEIE) for use in IPLEDs are introduced, and the roles of the ILs in IPLEDs comparing these with a conventional Cs2CO3 IL are elucidated. These polymer ILs can reduce the electron injection barrier between ZnO and emitting layer by decreasing the work function (WF) of underlying ZnO, thereby effectively facilitating electron injection into the emitting layer. WF of ZnO covered by PEI is found to be lower than that covered by PEIE due to higher N+/C ratio of PEI. Furthermore, they can block the quenching of excitons and increase the luminous efficiency of devices. Thus, IPLEDs with PEI IL of optimum thickness (8 nm) show current efficiency (13.5 cd A–1), which is dramatically higher than that of IPLEDs with a Cs2CO3 IL (8 cd A‐1).
Efficient and air‐stable inverted polymer‐light emitting diodes (IPLEDs) can be realized by using insulating polymer electron‐injecting interlayers (ILs), branched polyethyleneimine (PEI), and polyethyleneimine ethoxylated (PEIE), giving highest current efficiencies of 13.5 cd A‐1 and 12 cd A‐1, respectively. Polymer ILs can facilitate electron injection into emitting layer as well as block the exciton quenching.
Immunotoxins (ITs), which are toxin-fused tumor antigen-specific antibody chimeric proteins, have been developed to selectively kill targeted cancer cells. The epidermal growth factor receptor (EGFR) ...is an attractive target for the development of anti-EGFR ITs against solid tumors due to its overexpression on the cell surface of various solid tumors. However, the low basal level expression of EGFR in normal tissue cells can cause undesirable on-target/off-tumor toxicity and reduce the therapeutic window of anti-EGFR ITs. Here, based on an anti-EGFR monobody with cross-reactivity to both human and murine EGFR, we developed a strategy to tailor the anti-EGFR affinity of the monobody-based ITs carrying a 24-kDa fragment of
exotoxin A (PE24), termed ER-PE24, to distinguish tumors that overexpress EGFR from normal tissues. Five variants of ER-PE24 were generated with different EGFR affinities (
≈ 0.24 nM to 104 nM), showing comparable binding activity for both human and murine EGFR. ER/0.2-PE24 with the highest affinity (
≈ 0.24 nM) exhibited a narrow therapeutic window of 19 pM to 93 pM, whereas ER/21-PE24 with an intermediate affinity (
≈ 21 nM) showed a much broader therapeutic window of 73 pM to 1.5 nM in in vitro cytotoxic assays using tumor model cell lines. In EGFR-overexpressing tumor xenograft mouse models, the maximum tolerated dose (MTD) of intravenous injection of ER/21-PE24 was found to be 0.4 mg/kg, which was fourfold higher than the MTD (0.1 mg/kg) of ER/0.2-PE24. Our study provides a strategy for the development of IT targeting tumor overexpressed antigens with basal expression in broad normal tissues by tailoring tumor antigen affinities.
Many studies have focused on global hypomethylation or hypermethylation of tumor suppressor genes, but less is known about the impact of promoter hypomethylation of oncogenes. We previously showed ...that promoter methylation may gradually increase or decrease during the transition from gastric mucosa (GM) to intestinal metaplasia (IM) to gastric cancer (GC). In our study, we focused on regional CpG hypomethylation of the promoter‐proximal DNA of the transcription factor ONECUT2 (OC2) in IM and GC cells. We validated the hypomethylation of promoter‐proximal DNA of OC2 in 160 primary GCs, in which methylation level correlated negatively with OC2 mRNA level. IM and GC cells stained positively for OC2, whereas GM cells did not. Stable transfection of OC2 in GC cells promoted colony formation, cell migration, invasion and proliferation. Moreover, OC2 knockdown with a short hairpin RNA suppressed tumorigenesis in nude mice. In addition, chromatin immunoprecipitation coupled with DNA sequencing and RNA‐seq analyses revealed that OC2 triggered ACSL5, which is strongly expressed in IM of the stomach but not in GM, indicating that OC2 and ACSL5 are early‐stage biomarkers for GC. We also observed a high correlation between the levels of OC2 and ACSL5 mRNAs in the GENT database These results suggest that epigenetic alteration of OC2 upregulates its expression, which then activates ACSL5; thus, OC2 is induced in IM by epigenetic alteration and triggers ACSL5 expression, and thus OC2 and ACSL5 may cooperatively promote intestinal differentiation and GC progression.
What's new?
DNA hypomethylation can promote cancer development through activation of genes with oncogenic potential. Here, the authors found that CpGs in the promoter‐proximal DNA of ONECUT2 were hypomethylated in intestinal metaplasia and gastric cancers, and that hypomethylation was associated with ONECUT2 upregulation. Functional analysis demonstrated that ONECUT2 has oncogenic potential and could activate ACSL5, which is also expressed in intestinal metaplasia, suggesting that ONECUT2 and ACSL5 may cooperate to promote intestinal differentiation or development of gastric cancer. Taken together, the findings suggest that ONECUT2 and its downstream target ACSL5 could be used to develop early detection biomarkers and prevent gastric carcinogenesis.
Assessing atomic defect states and their ramifications on the electronic properties of two-dimensional van der Waals semiconducting transition metal dichalcogenides (SC-TMDs) is the primary task to ...expedite multi-disciplinary efforts in the promotion of next-generation electrical and optical device applications utilizing these low-dimensional materials. Here, with electron tunneling and optical spectroscopy measurements with density functional theory, we spectroscopically locate the mid-gap states from chalcogen-atom vacancies in four representative monolayer SC-TMDs-WS
, MoS
, WSe
, and MoSe
-, and carefully analyze the similarities and dissimilarities of the atomic defects in four distinctive materials regarding the physical origins of the missing chalcogen atoms and the implications to SC-mTMD properties. In addition, we address both quasiparticle and optical energy gaps of the SC-mTMD films and find out many-body interactions significantly enlarge the quasiparticle energy gaps and excitonic binding energies, when the semiconducting monolayers are encapsulated by non-interacting hexagonal boron nitride layers.
Controlled alignment and patterning of individual semiconducting nanowires at a desired position in a large area is a key requirement for electronic device applications. High-speed, large-area ...printing of highly aligned individual nanowires that allows control of the exact numbers of wires, and their orientations and dimensions is a significant challenge for practical electronics applications. Here we use a high-speed electrohydrodynamic organic nanowire printer to print large-area organic semiconducting nanowire arrays directly on device substrates in a precisely, individually controlled manner; this method also enables sophisticated large-area nanowire lithography for nano-electronics. We achieve a maximum field-effect mobility up to 9.7 cm(2) V(-1) s(-1) with extremely low contact resistance (<5.53 Ω cm), even in nano-channel transistors based on single-stranded semiconducting nanowires. We also demonstrate complementary inverter circuit arrays comprising well-aligned p-type and n-type organic semiconducting nanowires. Extremely fast nanolithography using printed semiconducting nanowire arrays provide a simple, reliable method of fabricating large-area and flexible nano-electronics.
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