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1.
Nat Methods ; 20(5): 735-746, 2023 05.
Article in English | MEDLINE | ID: mdl-37024654

ABSTRACT

High-speed three-dimensional (3D) intravital imaging in animals is useful for studying transient subcellular interactions and functions in health and disease. Light-field microscopy (LFM) provides a computational solution for snapshot 3D imaging with low phototoxicity but is restricted by low resolution and reconstruction artifacts induced by optical aberrations, motion and noise. Here, we propose virtual-scanning LFM (VsLFM), a physics-based deep learning framework to increase the resolution of LFM up to the diffraction limit within a snapshot. By constructing a 40 GB high-resolution scanning LFM dataset across different species, we exploit physical priors between phase-correlated angular views to address the frequency aliasing problem. This enables us to bypass hardware scanning and associated motion artifacts. Here, we show that VsLFM achieves ultrafast 3D imaging of diverse processes such as the beating heart in embryonic zebrafish, voltage activity in Drosophila brains and neutrophil migration in the mouse liver at up to 500 volumes per second.


Subject(s)
Microscopy , Zebrafish , Animals , Mice , Imaging, Three-Dimensional/methods
2.
Opt Express ; 32(12): 20571-20588, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859436

ABSTRACT

Frequency-scanning interferometry (FSI) utilizing external cavity diode lasers (ECDL) stands out as a potent technique for absolute distance measurement. Nevertheless, the inherent scanning nonlinearity of ECDL and phase noise pose a challenge, as it can compromise the accuracy of phase extraction from interference signals, thereby reducing the measurement accuracy of FSI. In this study, we propose a composite algorithm aimed at mitigating non-orthogonal errors by integrating the least-squares and Heydemann correction technique. Furthermore, we employ Kalman filtering for precise phase tracking. We introduce a parameter selection strategy based on the statistical distribution of instantaneous frequency to achieve the fusion estimation of phase observation values and theoretical models, which starts a new perspective for the application of multi-dimensional data fusion in FSI measurement. Through simulation and experimental validation, the efficacy of this approach is confirmed. The experimental results show promising outcomes: with an average phase error of 0.12%, a standard deviation of less than 1.7 µm in absolute distance measurement, and an average positioning accuracy error of 0.29 µm.

3.
Anal Chem ; 95(26): 9901-9913, 2023 07 04.
Article in English | MEDLINE | ID: mdl-37310727

ABSTRACT

Candida albicans (C. albicans), a major fungal pathogen, causes life-threatening infections in immunocompromised individuals. Fluconazole (FLC) is recommended as first-line therapy for treatment of invasive fungal infections. However, the widespread use of FLC has resulted in increased antifungal resistance among different strains of Candida, especially C. albicans, which is a leading source of hospital-acquired infections. Here, by hyperspectral stimulated Raman scattering imaging of single fungal cells in the fingerprint window and pixel-wise spectral unmixing, we report aberrant ergosteryl ester accumulation in azole-resistant C. albicans compared to azole-susceptible species. This accumulation was a consequence of de novo lipogenesis. Lipid profiling by mass spectroscopy identified ergosterol oleate to be the major species stored in azole-resistant C. albicans. Blocking ergosterol esterification by oleate and suppressing sterol synthesis by FLC synergistically suppressed the viability of C. albicans in vitro and limited the growth of biofilm on mouse skin in vivo. Our findings highlight a metabolic marker and a new therapeutic strategy for targeting azole-resistant C. albicans by interrupting the esterified ergosterol biosynthetic pathway.


Subject(s)
Antifungal Agents , Candida albicans , Animals , Mice , Antifungal Agents/chemistry , Azoles/pharmacology , Azoles/metabolism , Spectrum Analysis, Raman , Esters/metabolism , Oleic Acid/metabolism , Microbial Sensitivity Tests , Fluconazole/metabolism , Ergosterol/pharmacology , Ergosterol/metabolism
4.
Plant Biotechnol J ; 21(4): 819-838, 2023 04.
Article in English | MEDLINE | ID: mdl-36597711

ABSTRACT

Plant architecture and stress tolerance play important roles in rice breeding. Specific leaf morphologies and ideal plant architecture can effectively improve both abiotic stress resistance and rice grain yield. However, the mechanism by which plants simultaneously regulate leaf morphogenesis and stress resistance remains elusive. Here, we report that SRL10, which encodes a double-stranded RNA-binding protein, regulates leaf morphology and thermotolerance in rice through alteration of microRNA biogenesis. The srl10 mutant had a semi-rolled leaf phenotype and elevated sensitivity to high temperature. SRL10 directly interacted with catalase isozyme B (CATB), and the two proteins mutually increased one other's stability to enhance hydrogen peroxide (H2 O2 ) scavenging, thereby contributing to thermotolerance. The natural Hap3 (AGC) type of SRL10 allele was found to be present in the majority of aus rice accessions, and was identified as a thermotolerant allele under high temperature stress in both the field and the growth chamber. Moreover, the seed-setting rate was 3.19 times higher and grain yield per plant was 1.68 times higher in near-isogenic line (NIL) carrying Hap3 allele compared to plants carrying Hap1 allele under heat stress. Collectively, these results reveal a new locus of interest and define a novel SRL10-CATB based regulatory mechanism for developing cultivars with high temperature tolerance and stable yield. Furthermore, our findings provide a theoretical basis for simultaneous breeding for plant architecture and stress resistance.


Subject(s)
Oryza , Thermotolerance , Thermotolerance/genetics , Oryza/metabolism , Catalase/genetics , Catalase/metabolism , Isoenzymes/metabolism , Plant Breeding , Edible Grain , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism
5.
Opt Express ; 31(25): 41202-41218, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38087525

ABSTRACT

Optical coherence tomography (OCT) is a label-free, non-invasive 3D imaging tool widely used in both biological research and clinical diagnosis. Conventional OCT modalities can only visualize specimen tomography without chemical information. Here, we report a bond-selective full-field OCT (BS-FF-OCT), in which a pulsed mid-infrared laser is used to modulate the OCT signal through the photothermal effect, achieving label-free bond-selective 3D sectioned imaging of highly scattering samples. We first demonstrate BS-FF-OCT imaging of 1 µm PMMA beads embedded in agarose gel. Next, we show 3D hyperspectral imaging of up to 75 µm of polypropylene fiber mattress from a standard surgical mask. We then demonstrate BS-FF-OCT imaging on biological samples, including cancer cell spheroids and C. elegans. Using an alternative pulse timing configuration, we finally demonstrate the capability of BS-FF-OCT on imaging a highly scattering myelinated axons region in a mouse brain tissue slice.


Subject(s)
Caenorhabditis elegans , Tomography, Optical Coherence , Animals , Mice , Tomography, Optical Coherence/methods , Imaging, Three-Dimensional
6.
Phys Rev Lett ; 131(24): 246301, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38181146

ABSTRACT

Valleytronics is a research field utilizing a valley degree of freedom of electrons for information processing and storage. A strong valley polarization is critical for realistic valleytronic applications. Here, we predict a tunneling valley Hall effect (TVHE) driven by tilted Dirac fermions in all-in-one tunnel junctions based on a two-dimensional (2D) valley material. Different doping of the electrode and spacer regions in these tunnel junctions results in momentum filtering of the tunneling Dirac fermions, generating a strong transverse valley Hall current dependent on the Dirac-cone tilting. Using the parameters of an existing 2D valley material, we demonstrate that such a strong TVHE can host a giant valley Hall angle even in the absence of the Berry curvature. Finally, we predict that resonant tunneling can occur in a tunnel junction with properly engineered device parameters such as the spacer width and transport direction, providing significant enhancement of the valley Hall angle. Our work opens a new approach to generate valley polarization in realistic valleytronic systems.

7.
Phys Rev Lett ; 130(21): 216702, 2023 May 26.
Article in English | MEDLINE | ID: mdl-37295086

ABSTRACT

Ferromagnets are known to support spin-polarized currents that control various spin-dependent transport phenomena useful for spintronics. On the contrary, fully compensated antiferromagnets are expected to support only globally spin-neutral currents. Here, we demonstrate that these globally spin-neutral currents can represent the Néel spin currents, i.e., staggered spin currents flowing through different magnetic sublattices. The Néel spin currents emerge in antiferromagnets with strong intrasublattice coupling (hopping) and drive the spin-dependent transport phenomena such as tunneling magnetoresistance (TMR) and spin-transfer torque (STT) in antiferromagnetic tunnel junctions (AFMTJs). Using RuO_{2} and Fe_{4}GeTe_{2} as representative antiferromagnets, we predict that the Néel spin currents with a strong staggered spin polarization produce a sizable fieldlike STT capable of the deterministic switching of the Néel vector in the associated AFMTJs. Our work uncovers the previously unexplored potential of fully compensated antiferromagnets and paves a new route to realize the efficient writing and reading of information for antiferromagnetic spintronics.

8.
Bioorg Med Chem ; 83: 117240, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36963270

ABSTRACT

Protein tyrosine phosphatase (PTP1B) antagonizes insulin signaling and acts as a potential therapeutic target for insulin resistance associated with obesity and type II diabetes. In this work, a series of isosteviol derivatives 1-28 was synthesized and the inhibitory activity on PTP1B was evaluated by double antibody sandwich ELISA (DAS-ELISA) in vitro. Most isosteviol derivatives showed moderate PTP1B inhibitory activities. Among them, derivatives 10, 13, 24, 27 showed remarkable bioactivities with IC50 values ranging from 0.24 to 0.40 µM. Particularly, derivative 24 exhibited the best inhibitory activity against PTP1B (IC50 = 0.24 µM) in vitro; moreover, it showed 7-fold selectivity to PTP1B over T-cell protein tyrosine phosphatase (TCPTP) and 14-fold selectivity to PTP1B over cell division cycle 25 homolog B (CDC25B). Molecular docking studies demonstrated the hydrogen bond interaction between 24 and LYS-116 residue in PTP1B might be essential for the inhibitory activity. The results suggested that derivative 24 has great potential to be employed as drug candidate for the treatment of obesity and type II diabetes.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Molecular Docking Simulation , Structure-Activity Relationship , Diabetes Mellitus, Type 2/drug therapy , Enzyme Inhibitors/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Obesity/drug therapy
9.
Phys Chem Chem Phys ; 25(27): 18048-18055, 2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37378660

ABSTRACT

In this study, polarization Raman spectra were collected for binary mixtures of formic acid/methanol and formic acid/acetonitrile with different volume fractions. The broad band of formic acid in the CO vibration region was divided into four vibration peaks, corresponding to CO symmetric and anti-symmetric stretching vibration from cyclic dimer, CO stretching from open dimer, and CO stretching from the free monomer. The experiments showed that as the volume fraction of formic acid in the binary mixture decreased, the cyclic dimer gradually converted to the open dimer, and at a volume fraction of 0.1, fully depolymerized into monomer form (free monomer, solvated monomer, and hydrogen bonding monomer clusters with solvent). The contribution percentage of the total CO stretching intensity of each structure at different concentrations was quantitatively calculated using high resolution infrared spectroscopy, and the results were consistent with the conclusions predicted by polarization Raman spectroscopy. Concentration-triggered 2D-COS synchronous and asynchronous spectra also confirmed the kinetics of formic acid diluted in acetonitrile. This work provides a spectroscopic method for studying the structure of organic compounds in solution and concentration-triggering kinetics in mixtures.

10.
Phys Chem Chem Phys ; 25(20): 13999-14004, 2023 May 24.
Article in English | MEDLINE | ID: mdl-37194330

ABSTRACT

To explain the polarization Raman noncoincidence effect of specific polar bonds and the noncoincidence phenomenon between FT-Raman and FT-IR spectra, aggregation-induced spectral splitting theory was proposed. In this paper, the vibration splitting theory was demonstrated using two strategies: improving the spectral resolution with cryogenic matrix isolation techniques and identifying cases where the coupling splitting is large enough to be distinguishable. The monomer and dimer splitting bands of acetone were detected when cryogenically isolated by the Ar matrix. Additionally, the polarization Raman and two-dimensional infrared spectra of a ß-propiolactone (PIL)/CCl4 binary mixture were collected at room temperature, and the spectral splitting phenomenon was clearly observed. The dynamic transformation between the monomer and dimer could be achieved and detected by adjusting the PIL concentration. The observed splitting phenomenon was further confirmed by theoretical DFT calculations based on the monomer and dimer of PIL, as well as the FT-IR and FT-Raman spectra of PIL. Concentration-triggered 2D-COS synchronous and asynchronous spectra also confirmed the splitting phenomenon and the dilution kinetics of PIL/CCl4.

11.
Opt Express ; 30(20): 37112-37123, 2022 Sep 26.
Article in English | MEDLINE | ID: mdl-36258628

ABSTRACT

Stimulated Raman projection tomography is a label-free volumetric chemical imaging technology allowing three-dimensional (3D) reconstruction of chemical distribution in a biological sample from the angle-dependent stimulated Raman scattering projection images. However, the projection image acquisition process requires rotating the sample contained in a capillary glass held by a complicated sample rotation stage, limiting the volumetric imaging speed, and inhibiting the study of living samples. Here, we report a tilt-angle stimulated Raman projection tomography (TSPRT) system which acquires angle-dependent projection images by utilizing tilt-angle beams to image the sample from different azimuth angles sequentially. The TSRPT system, which is free of sample rotation, enables rapid scanning of different views by a tailor-designed four-galvo-mirror scanning system. We present the design of the optical system, the theory, and calibration procedure for chemical tomographic reconstruction. 3D vibrational images of polystyrene beads and C. elegans are demonstrated in the C-H vibrational region.


Subject(s)
Caenorhabditis elegans , Polystyrenes , Animals , Tomography/methods , Tomography, X-Ray Computed , Imaging, Three-Dimensional/methods , Image Processing, Computer-Assisted
12.
Toxicol Appl Pharmacol ; 448: 116098, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35662663

ABSTRACT

Drug-induced liver injury (DILI) has increased in recent years, leading to acute liver failure. 3,3',5-triiodo-l-thyronine (T3) has been reported to exert a potent hepatoprotective effect. However, the mechanism and efficacy of T3 on DILI remain undocumented. In this study, an MTT assay was used to detect the effect of T3 on hepatotoxicity of acetaminophen (APAP) in L02 cells. Then, we screened key targets and related biological pathways by network pharmacology. Finally, enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to verify the mechanism and key targets of T3 on DILI. The results of the MTT assay showed that T3 significantly decreased hepatocellular injury induced by APAP. Network pharmacology and bioinformatics analysis showed that 118 intersection targets of T3 and DILI were identified and the mechanism of T3 on DILI was related to cell proliferation and oxidative stress. ELISA results showed that T3 may be an effective treatment for DILI as biomarkers of hepatocellular injury such as AST, ALP were decreased compared to APAP only treated cells, and the mechanism of T3 may be mediated in part through improving redox balance. The topological parameter screening results suggested 12 key targets of T3 for DILI. Among them, PPARα is associated with DILI, and activation of PPARα can reduce oxidative stress and cell necrosis. Therefore, PPARα was identified as a target for verification. qRT-PCR analysis demonstrated that T3 could reverse the down-regulation of PPARα induced by APAP exposure. Taken together, we demonstrated for the first time that T3 could activate PPARα, promote cell proliferation and reduce oxidative stress, and play a vital role in the treatment of DILI, which provides a reference for T3 as a candidate treatment for DILI.


Subject(s)
Chemical and Drug Induced Liver Injury , Liver Failure, Acute , Triiodothyronine , Acetaminophen/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Humans , Liver/drug effects , Liver Failure, Acute/chemically induced , Liver Failure, Acute/metabolism , Network Pharmacology , Oxidative Stress/drug effects , PPAR alpha/metabolism , Triiodothyronine/pharmacology
13.
Langmuir ; 38(27): 8266-8279, 2022 07 12.
Article in English | MEDLINE | ID: mdl-35749646

ABSTRACT

Peroxidase-like nanozymes with robust catalytic capacity and detection specificity have been proposed as substitutes to natural peroxidases in biochemical sensing. However, the catalytic activity enhancement, detection mechanism, and application of nanozyme-based biosensors toward l-cysteine (l-Cys) detection still remain significant challenges. In this work, a doped ferrite nanozyme with well-defined structure and surface charges is fabricated by a two-step method of continuous flow coprecipitation and high-temperature annealing. The resulted ferrite nanozyme possesses an average size of 54.5 nm and a zeta-potential of 6.45 mV. A high-performance biosensor is manufactured based on the peroxidase-like catalytic feature of the doped ferrite. The ferrite nanozyme can oxidize the 3,3',5,5'-tetramethylbenzidine (TMB) with the assistance of H2O2 because of the instinctive capacity to decompose H2O2 into ·OH. The Michaelis-Menten constants (0.0911 mM for TMB, 0.140 mM for H2O2) of the ferrite nanozyme are significantly smaller than those of horseradish peroxidase. A reliable colorimetric method is established to selectively analyze l-Cys via a facile mixing-and-detecting methodology. The detection limit and linear range are 0.119 µM and 0.2-20 µM, respectively. Taking the merits of the ferrite nanozyme-based biosensors, the l-Cys level in the human serum can be qualitatively detected. It can be anticipated that the surface-charged ferrite nanozyme shows great application prospects in the fields of bioanalytical chemistry and point-of-care testing.


Subject(s)
Biosensing Techniques , Colorimetry , Colorimetry/methods , Cysteine , Ferric Compounds , Humans , Hydrogen Peroxide/chemistry , Peroxidase/chemistry , Peroxidases
14.
Dis Colon Rectum ; 65(8): 1062-1068, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35421009

ABSTRACT

BACKGROUND: Anastomotic stenosis is a common complication of colorectal cancer surgery with anastomosis. Transanal minimally invasive surgery is a novel approach to the treatment of anastomotic stenosis. OBJECTIVE: This study aimed to evaluate the efficacy and safety of transanal minimally invasive surgery for anastomotic stenosis treatment. DESIGN: This was a retrospective study. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: This study included patients with rectal anastomotic stenosis who after undergoing colorectal surgery were admitted to the Sir Run Run Shaw Hospital between September 2017 and June 2019. MAIN OUTCOME MEASURES: The primary outcome was the operative success rate. The secondary outcomes were intraoperative variables, postoperative complications, stoma closure conditions, and stenosis recurrence risks. RESULTS: Nine patients, aged 52 to 80 years, with a history of colorectal cancer with end-to-end anastomosis underwent transanal minimally invasive surgery for anastomotic stenosis. The distance between the stenosis and the anal verge ranged from 5 to 12 cm. The mean stenosis diameter was 0.3 cm. Four patients had completely obstructed rectal lumens. Eight of 9 patients successfully underwent transanal minimally invasive surgery radial incision and cutting. The average operation time was 50 minutes. After the procedure, 1 patient had symptomatic procedure-associated perforations but recovered with conservative treatment. No perioperative mortality occurred. One patient underwent transverse colostomy 1 month after transanal minimally invasive surgery because of proximal colon ischemia induced by primary rectal surgery. Eight patients underwent protective loop ileostomy. After transanal minimally invasive surgery, stoma closure was performed in 88% of patients with no stenosis recurrence or obstruction at follow-up (21-42 mo). LIMITATIONS: This study was limited by its small sample size and single-center design. CONCLUSIONS: Transanal minimally invasive surgery provides an excellent operative field, good maneuverability, and versatile instrumentation and is a safe and effective treatment for rectal anastomotic stenosis, especially for severe fibrotic stenosis or complete obstruction. See Dynamic Article Video at http://links.lww.com/DCR/B965 .


Subject(s)
Rectal Neoplasms , Transanal Endoscopic Surgery , Anal Canal/surgery , Anastomosis, Surgical/adverse effects , Anastomotic Leak/etiology , Anastomotic Leak/surgery , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Humans , Postoperative Complications , Rectal Neoplasms/surgery , Rectum/surgery , Retrospective Studies , Transanal Endoscopic Surgery/adverse effects
15.
Anal Chem ; 93(47): 15703-15711, 2021 11 30.
Article in English | MEDLINE | ID: mdl-34787995

ABSTRACT

Spectroscopic stimulated Raman scattering (SRS) imaging has become a useful tool finding a broad range of applications. Yet, wider adoption is hindered by the bulky and environmentally sensitive solid-state optical parametric oscillator (OPO) in a current SRS microscope. Moreover, chemically informative multiwindow SRS imaging across C-H, C-D, and fingerprint Raman regions is challenging due to the slow wavelength tuning speed of the solid-state OPO. In this work, we present a multiwindow SRS imaging system based on a compact and robust fiber laser with rapid and wide tuning capability. To address the relative intensity noise intrinsic to a fiber laser, we implemented autobalanced detection, which enhances the signal-to-noise ratio of stimulated Raman loss imaging by 23 times. We demonstrate high-quality SRS metabolic imaging of fungi, cancer cells, and Caenorhabditis elegans across the C-H, C-D, and fingerprint Raman windows. Our results showcase the potential of the compact multiwindow SRS system for a broad range of applications.


Subject(s)
Lasers , Spectrum Analysis, Raman , Diagnostic Tests, Routine , Microscopy , Signal-To-Noise Ratio
16.
Small ; 17(43): e2103780, 2021 10.
Article in English | MEDLINE | ID: mdl-34643028

ABSTRACT

Optical imaging in the second near infrared region (NIR-II, 1000-1700 nm) provides higher resolution and deeper penetration depth for accurate and real-time vascular anatomy, blood dynamics, and function information, effectively contributing to the early diagnosis and curative effect assessment of vascular anomalies. Currently, NIR-II optical imaging demonstrates encouraging results including long-term monitoring of vascular injury and regeneration, real-time feedback of blood perfusion, tracking of lymphatic metastases, and imaging-guided surgery. This review summarizes the latest progresses of NIR-II optical imaging for angiography including fluorescence imaging, photoacoustic (PA) imaging, and optical coherence tomography (OCT). The development of current NIR-II fluorescence, PA, and OCT probes (i.e., single-walled carbon nanotubes, quantum dots, rare earth doped nanoparticles, noble metal-based nanostructures, organic dye-based probes, and semiconductor polymer nanoparticles), highlighting probe optimization regarding high brightness, longwave emission, and biocompatibility through chemical modification or nanotechnology, is first introduced. The application of NIR-II probes in angiography based on the classification of peripheral vascular, cerebrovascular, tumor vessel, and cardiovascular, is then reviewed. Major challenges and opportunities in the NIR-II optical imaging for vascular imaging are finally discussed.


Subject(s)
Metals, Rare Earth , Nanoparticles , Nanotubes, Carbon , Quantum Dots , Infrared Rays , Optical Imaging
17.
Anticancer Drugs ; 31(10): 1018-1025, 2020 11.
Article in English | MEDLINE | ID: mdl-33009035

ABSTRACT

X-inactive-specific transcript (XIST) is a 19 kb noncoding RNA which is oncogenic in many cancers including gastric cancer. It is reported that XIST contributes to gastric cancer cells resistant to cisplatin, but specific mechanisms governing this resistance remain unclear. We firstly examined the XIST level in gastric cancer cells and tumor specimens. We confirmed that XIST is overexpressed in gastric cancer cells and tumors, which further contributed to the poor prognosis of patients with gastric cancer. We also confirmed that high XIST level contributes to the cisplatin resistance in gastric cancer cells. Subsequently, we predicted microRNAs that have the potential to interact with XIST and found that Let-7b-5p may directly interact with XIST. We confirmed the direct interaction between XIST and Let-7b-5p and identified a negative correlation between the level of Let-7b-5p and XIST in gastric cancer tumors. Meanwhile, Let-7b-5p inhibitor treatment can partially rescued the effect of XIST-specific small interfering RNA on cell proliferation and apoptosis by regulating Aurora kinase B expression. XIST functions as an oncogene in gastric cancer which contributes to the cisplatin resistance by interacting with Let-7b-5p.


Subject(s)
Cisplatin/pharmacology , Drug Resistance, Neoplasm/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Stomach Neoplasms/drug therapy , Aged , Antineoplastic Agents/pharmacology , Aurora Kinase B/genetics , Case-Control Studies , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Middle Aged , Prognosis , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality
18.
J Pharmacol Exp Ther ; 370(3): 593-601, 2019 09.
Article in English | MEDLINE | ID: mdl-31126978

ABSTRACT

The global prevalence of neurologic disorders is rising, and yet we are still unable to deliver most drug molecules, in therapeutic quantities, to the brain. The blood brain barrier consists of a tight layer of endothelial cells surrounded by astrocyte foot processes, and these anatomic features constitute a significant barrier to drug transport from the blood to the brain. One way to bypass the blood brain barrier and thus treat diseases of the brain is to use the nasal route of administration and deposit drugs at the olfactory region of the nares, from where they travel to the brain via mechanisms that are still not clearly understood, with travel across nerve fibers and travel via a perivascular pathway both being hypothesized. The nose-to-brain route has been demonstrated repeatedly in preclinical models, with both solution and particulate formulations. The nose-to-brain route has also been demonstrated in human studies with solution and particle formulations. The entry of device manufacturers into the arena will enable the benefits of this delivery route to become translated into approved products. The key factors that determine the efficacy of delivery via this route include the following: delivery to the olfactory area of the nares as opposed to the respiratory region, a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia, and a reduction in drug metabolism in the nasal cavity. Indications where nose-to-brain products are likely to emerge first include the following: neurodegeneration, post-traumatic stress disorder, pain, and glioblastoma.


Subject(s)
Administration, Intranasal/methods , Brain/metabolism , Drug Delivery Systems/methods , Nose , Animals , Humans , Nasal Cavity/metabolism , Nasal Mucosa/metabolism
19.
J Am Chem Soc ; 140(28): 8877-8886, 2018 07 18.
Article in English | MEDLINE | ID: mdl-29952571

ABSTRACT

Developing excited-state intramolecular proton transfer (ESIPT) emitters with high photoluminescence quantum yields (ΦPLs) and long fluorescence lifetimes in solid state remains a formidable challenge. In this study, we integrated the molecular design tactics of thermally activated delayed fluorescence (TADF) into ESIPT molecules with the goals of improving their ΦPLs and increasing their fluorescence lifetimes. Two proof-of-concept molecules, PXZPDO and DMACPDO, were developed by adopting symmetric D-π-A-π-D molecular architectures (where D and A represent donors and acceptors, respectively) featuring electron-donating phenoxazine or a 9,9-dimethyl-9,10-dihydroacridine moiety, an ESIPT core ß-diketone, and phenylene π-bridges. Both molecules exhibited sole enol-type forms stabilized by intramolecular hydrogen bonds and exhibited a unique and dynamic ESIPT character that was verified by transient absorption analyses. Endowed with distinct TADF features, PXZPDO and DMACPDO showed high ΦPLs of 68% and 86% in the film state, coupled with notable delayed fluorescence lifetimes of 1.33 and 1.94 µs, respectively. Employing these ESIPT emitters successfully achieved maximum external quantum efficiencies (ηexts) of 18.8% and 23.9% for yellow and green organic light-emitting diodes (OLEDs), respectively, which represent the state-of-the-art device performances for ESIPT emitters. This study not only opens a new avenue for designing efficient ESIPT emitters with high ΦPLs and long fluorescence lifetimes in solid state but also unlocks the huge potential of ESIPT emitters in realizing high-efficiency OLEDs.

20.
Sensors (Basel) ; 18(8)2018 Jul 27.
Article in English | MEDLINE | ID: mdl-30060539

ABSTRACT

The adaptive coordination of trust services can provide highly dependable and personalized solutions for industrial requirements in the service-oriented industrial internet of things (IIoT) architecture to achieve efficient utilization of service resources. Although great progress has been made, trust service coordination still faces challenging problems such as trustless industry service, poor coordination, and quality of service (QoS) personalized demand. In this paper, we propose a QoS-driven and adaptive trust service coordination method to implement Pareto-efficient allocation of limited industrial service resources in the background of the IIoT. First, we established a Pareto-effective and adaptive industrial IoT trust service coordination model and introduced a blockchain-based adaptive trust evaluation mechanism to achieve trust evaluation of industrial services. Then, taking advantage of a large and complex search space for solution efficiency, we introduced and compared multi-objective gray-wolf algorithms with the particle swarm optimization (PSO) and dragonfly algorithms. The experimental results showed that by judging and blacklisting malicious raters quickly and accurately, our model can efficiently realize self-adaptive, personalized, and intelligent trust service coordination under the given constraints, improving not only the response time, but also the success rate in coordination.

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