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1.
PLoS One ; 19(5): e0301134, 2024.
Article in English | MEDLINE | ID: mdl-38743645

ABSTRACT

Land cover classification (LCC) is of paramount importance for assessing environmental changes in remote sensing images (RSIs) as it involves assigning categorical labels to ground objects. The growing availability of multi-source RSIs presents an opportunity for intelligent LCC through semantic segmentation, offering a comprehensive understanding of ground objects. Nonetheless, the heterogeneous appearances of terrains and objects contribute to significant intra-class variance and inter-class similarity at various scales, adding complexity to this task. In response, we introduce SLMFNet, an innovative encoder-decoder segmentation network that adeptly addresses this challenge. To mitigate the sparse and imbalanced distribution of RSIs, we incorporate selective attention modules (SAMs) aimed at enhancing the distinguishability of learned representations by integrating contextual affinities within spatial and channel domains through a compact number of matrix operations. Precisely, the selective position attention module (SPAM) employs spatial pyramid pooling (SPP) to resample feature anchors and compute contextual affinities. In tandem, the selective channel attention module (SCAM) concentrates on capturing channel-wise affinity. Initially, feature maps are aggregated into fewer channels, followed by the generation of pairwise channel attention maps between the aggregated channels and all channels. To harness fine-grained details across multiple scales, we introduce a multi-level feature fusion decoder with data-dependent upsampling (MLFD) to meticulously recover and merge feature maps at diverse scales using a trainable projection matrix. Empirical results on the ISPRS Potsdam and DeepGlobe datasets underscore the superior performance of SLMFNet compared to various state-of-the-art methods. Ablation studies affirm the efficacy and precision of SAMs in the proposed model.


Subject(s)
Remote Sensing Technology , Remote Sensing Technology/methods , Algorithms , Image Processing, Computer-Assisted/methods , Neural Networks, Computer
2.
Ren Fail ; 46(1): 2338483, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38604948

ABSTRACT

BACKGROUND: Previous study consistently showed that lower serum sodium (SNa) was associated with a greater risk of mortality in hemodialysis (HD) patients. However, few studies have focused on the change in SNa (ΔSNa = post-HD SNa - pre-HD SNa) during an HD session. METHODS: In a retrospective cohort of maintenance HD adults, all-cause mortality and cardio-cerebrovascular event (CCVE) were followed up for a medium of 82 months. Baseline pre-HD SNa and ΔSNa were collected; time-averaged pre-HD SNa and ΔSNa were computed as the mean values within 1-year, 2-year and 3-year intervals after enrollment. Cox proportional hazards models were used to evaluate the relationships of pre-HD and ΔSNa with outcomes. RESULTS: Time-averaged pre-HD SNa were associated with all-cause mortality (2-year pre-HD SNa: HR [95% CI] 0.86 [0.74-0.99], p = 0.042) and CCVE (3-year pre-HD SNa: HR [95% CI] 0.83 [0.72-0.96], p = 0.012) with full adjustment. Time-averaged ΔSNa also demonstrated an association with all-cause mortality (3-year ΔSNa: HR [95% CI] 1.26 [1.03-1.55], p = 0.026) as well as with CCVE (3-year ΔSNa: HR [95% CI] 1.51 [1.21-1.88], p = <0.001) when fully adjusted. Baseline pre-HD SNa and ΔSNa didn't exhibit association with both outcomes. CONCLUSIONS: Lower time-averaged pre-HD SNa and higher time-averaged ΔSNa were associated with a greater risk of all-cause mortality and CCVE in HD patients.


Subject(s)
Kidney Failure, Chronic , Sodium , Adult , Humans , Retrospective Studies , Renal Dialysis/adverse effects , Proportional Hazards Models
3.
Front Physiol ; 15: 1329145, 2024.
Article in English | MEDLINE | ID: mdl-38426209

ABSTRACT

Background: Manual bone age assessment (BAA) is associated with longer interpretation time and higher cost and variability, thus posing challenges in areas with restricted medical facilities, such as the high-altitude Tibetan Plateau. The application of artificial intelligence (AI) for automating BAA could facilitate resolving this issue. This study aimed to develop an AI-based BAA model for Han and Tibetan children. Methods: A model named "EVG-BANet" was trained using three datasets, including the Radiology Society of North America (RSNA) dataset (training set n = 12611, validation set n = 1425, and test set n = 200), the Radiological Hand Pose Estimation (RHPE) dataset (training set n = 5491, validation set n = 713, and test set n = 79), and a self-established local dataset [training set n = 825 and test set n = 351 (Han n = 216 and Tibetan n = 135)]. An open-access state-of-the-art model BoNet was used for comparison. The accuracy and generalizability of the two models were evaluated using the abovementioned three test sets and an external test set (n = 256, all were Tibetan). Mean absolute difference (MAD) and accuracy within 1 year were used as indicators. Bias was evaluated by comparing the MAD between the demographic groups. Results: EVG-BANet outperformed BoNet in the MAD on the RHPE test set (0.52 vs. 0.63 years, p < 0.001), the local test set (0.47 vs. 0.62 years, p < 0.001), and the external test set (0.53 vs. 0.66 years, p < 0.001) and exhibited a comparable MAD on the RSNA test set (0.34 vs. 0.35 years, p = 0.934). EVG-BANet achieved accuracy within 1 year of 97.7% on the local test set (BoNet 90%, p < 0.001) and 89.5% on the external test set (BoNet 85.5%, p = 0.066). EVG-BANet showed no bias in the local test set but exhibited a bias related to chronological age in the external test set. Conclusion: EVG-BANet can accurately predict the bone age (BA) for both Han children and Tibetan children living in the Tibetan Plateau with limited healthcare facilities.

4.
BMC Nephrol ; 24(1): 113, 2023 04 26.
Article in English | MEDLINE | ID: mdl-37101121

ABSTRACT

BACKGROUND: Short-term and long-term blood pressure variability (BPV) in hemodialysis (HD) population are risk factors of cardiovascular diseases (CVD) and all-cause mortality. There is no full consensus on the best BPV metric. We compared the prognostic role of intra-dialytic and visit-to-visit BPV metrics for CVD morbidity and all-cause mortality in HD patients. METHODS: A retrospective cohort of 120 patients on HD was followed up for 44 months. Systolic blood pressure (SBP) and baseline characteristics were collected for 3 months. We calculated intra-dialytic and visit-to-visit BPV metrics, including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV) and residual. The primary outcomes were CVD events and all-cause mortality. RESULTS: In Cox regression analysis, both intra-dialytic and visit-to-visit BPV metrics were associated with increased CVD events (intra-dialytic CV: HR 1.70, 95% CI 1.28-2.27, p < 0.01; visit-to-visit CV: HR 1.55, 95% CI 1.12-2.16, p < 0.01), but not associated with increased all-cause mortality (intra-dialytic CV: HR 1.32, 95% CI 0.99-1.76, p = 0.06; visit-to-visit CV: HR 1.22, 95% CI 0.91-1.63, p = 0.18). Overall, intra-dialytic BPV showed greater prognostic ability than visit-to-visit BPV for both CVD event (AUC of intra-dialytic BPV and visit-to-visit BPV metrics respectively: SD 0.686, 0.606; CV 0.672, 0.425; VIM 0.677, 0.581; ARV 0.684, 0.618; residual 0.652, 0.586) and all-cause mortality (SD 0.671, 0.608; CV 0.662, 0.575; VIM 0.669, 0.581; ARV 0.529, 0.588; residual 0.651, 0.602). CONCLUSION: Compared to visit-to-visit BPV, intra-dialytic BPV is a greater predictor of CVD event in HD patients. No obvious priority was found among various BPV metrics.


Subject(s)
Cardiovascular Diseases , Hypertension , Humans , Blood Pressure/physiology , Retrospective Studies , Renal Dialysis/adverse effects , Blood Pressure Determination , Risk Factors , Hypertension/epidemiology
5.
Emerg Microbes Infect ; 12(1): e2169198, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36655944

ABSTRACT

During a pandemic, effective vaccines are typically in short supply, particularly at onset intervals when the wave is accelerating. We conducted an observational, retrospective analysis of aggregated data from all patients who tested positive for SARS-CoV-2 during the waves caused by the Delta and Omicron variants, stratified based on their known previous infection and vaccination status, throughout the University of Texas Medical Branch (UTMB) network. Next, the immunity statuses within each medical parameter were compared to naïve individuals for the effective decrease of occurrence. Lastly, we conducted studies using mice and pre-pandemic human samples for IgG responses to viral nucleocapsid compared to spike protein toward showing a functional component supportive of the medical data results in relation to the immunity types. During the Delta and Omicron waves, both infection-induced and hybrid immunities were associated with a trend of equal or greater decrease of occurrence than vaccine-induced immunity in hospitalizations, intensive care unit admissions, and deaths in comparison to those without pre-existing immunity, with hybrid immunity often trending with the greatest decrease. Compared to individuals without pre-existing immunity, those vaccinated against SARS-CoV-2 had a significantly reduced incidence of COVID-19, as well as all subsequent medical parameters. Though vaccination best reduces health risks associated with initial infection toward acquiring immunity, our findings suggest infection-induced immunity is as or more effective than vaccination in reducing the severity of reinfection from the Delta or Omicron variants, which should inform public health response at pandemic onset, particularly when triaging towards the allotment of in-demand vaccinations.


Subject(s)
COVID-19 , Humans , Animals , Mice , Reinfection , SARS-CoV-2 , Retrospective Studies , Hospitalization
6.
J Am Chem Soc ; 144(33): 14992-14996, 2022 08 24.
Article in English | MEDLINE | ID: mdl-35929968

ABSTRACT

Rational design of covalent organic frameworks (COFs) to broaden their diversity is highly desirable but challenging due to the limited, expensive, and complex building blocks, especially compared with other easily available porous materials. In this work, we fabricated two novel bioinspired COFs, namely, NUS-71 and NUS-72, using reticular chemistry with ellagic acid and triboronic acid-based building blocks. Both COFs with AB stacking mode exhibit high acetylene (C2H2) adsorption capacity and excellent separation performance for C2H2/CO2 mixtures, which is significant but rarely explored using COFs. The impressive affinities for C2H2 appear to be related to the sandwich structure formed by C2H2 and the host framework via multiple host-guest interactions. This work not only represents a new avenue for the construction of low-cost COFs but also expands the variety of the COF family using natural biochemicals as building blocks for broad application.


Subject(s)
Metal-Organic Frameworks , Acetylene , Adsorption , Carbon Dioxide/chemistry , Metal-Organic Frameworks/chemistry , Porosity
7.
Methods Mol Biol ; 2410: 193-208, 2022.
Article in English | MEDLINE | ID: mdl-34914048

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Several vaccine candidates have been developed in response to the COVID-19 pandemic. One approach is to construct live-recombinant viruses expressing the SARS-CoV-2 spike protein (S) as vaccine candidates. The vesicular stomatitis virus (VSV) vector is a mature vaccine platform which was successfully developed as a vaccine against Ebola virus (EBOV), leading to its licensure by the Food and Drug Administration (FDA) in December 2019. Based on this work, we developed two live, replication-competent VSV-vectored vaccines against SARS-CoV-2: (1) a VSV expressing the S protein of SARS-CoV-2 and (2) a bivalent VSV expressing the S protein of SARS-CoV-2 and the glycoprotein (GP) of EBOV. This protocol describes the methodologies for the design, cloning, rescue, and preparation of these recombinant VSV vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccines, Synthetic , COVID-19/prevention & control , Ebolavirus/immunology , Humans , Pandemics , Spike Glycoprotein, Coronavirus/genetics , Vaccine Development , Vaccines, Attenuated
8.
JCI Insight ; 7(3)2022 02 08.
Article in English | MEDLINE | ID: mdl-34914635

ABSTRACT

Stromal cells are emerging as key drivers of autoimmunity, partially because they produce inflammatory chemokines that orchestrate inflammation. Chemokine expression is regulated transcriptionally but also through posttranscriptional mechanisms, the specific drivers of which are still incompletely defined. CCL2 (MCP1) is a multifunctional chemokine that drives myeloid cell recruitment. During experimental autoimmune encephalomyelitis (EAE), an IL-17-driven model of multiple sclerosis, CCL2 produced by lymph node (LN) stromal cells was essential for immunopathology. Here, we showed that Ccl2 mRNA upregulation in human stromal fibroblasts in response to IL-17 required the RNA-binding protein IGF-2 mRNA-binding protein 2 (IGF2BP2, IMP2), which is expressed almost exclusively in nonhematopoietic cells. IMP2 binds directly to CCL2 mRNA, markedly extending its transcript half-life, and is thus required for efficient CCL2 secretion. Consistent with this, Imp2-/- mice showed reduced CCL2 production in LNs during EAE, causing impairments in monocyte recruitment and Th17 cell polarization. Imp2-/- mice were fully protected from CNS inflammation. Moreover, deletion of IMP2 after EAE onset was sufficient to mitigate disease severity. These data showed that posttranscriptional control of Ccl2 in stromal cells by IMP2 was required to permit IL-17-driven progression of EAE pathogenesis.


Subject(s)
Autoimmunity , Encephalomyelitis, Autoimmune, Experimental/genetics , Gene Expression Regulation , RNA-Binding Proteins/genetics , Th17 Cells/immunology , Up-Regulation , Animals , Cells, Cultured , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Male , Mice , Mice, Inbred C57BL , RNA, Messenger/genetics , RNA-Binding Proteins/biosynthesis , Th17 Cells/pathology
9.
Emerg Microbes Infect ; 11(1): 351-367, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34964428

ABSTRACT

The emergence of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern threatens the efficacy of currently approved vaccines and authorized therapeutic monoclonal antibodies (MAbs). It is hence important to continue searching for SARS-CoV-2 broadly neutralizing MAbs and defining their epitopes. Here, we isolate 9 neutralizing mouse MAbs raised against the spike protein of a SARS-CoV-2 prototype strain and evaluate their neutralizing potency towards a panel of variants, including B.1.1.7, B.1.351, B.1.617.1, and B.1.617.2. By using a combination of biochemical, virological, and cryo-EM structural analyses, we identify three types of cross-variant neutralizing MAbs, represented by S5D2, S5G2, and S3H3, respectively, and further define their epitopes. S5D2 binds the top lateral edge of the receptor-binding motif within the receptor-binding domain (RBD) with a binding footprint centred around the loop477-489, and efficiently neutralizes all variant pseudoviruses, but the potency against B.1.617.2 was observed to decrease significantly. S5G2 targets the highly conserved RBD core region and exhibits comparable neutralization towards the variant panel. S3H3 binds a previously unreported epitope located within the evolutionarily stable SD1 region and is able to near equally neutralize all of the variants tested. Our work thus defines three distinct cross-variant neutralizing sites on the SARS-CoV-2 spike protein, providing guidance for design and development of broadly effective vaccines and MAb-based therapies.


Subject(s)
COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Epitope Mapping , Female , Humans , Mice , Mice, Inbred BALB C , Neutralization Tests , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
10.
Sci Immunol ; 6(66): eaao3669, 2021 Dec 17.
Article in English | MEDLINE | ID: mdl-34919443

ABSTRACT

Prior experience of pathogen-associated stimuli reduces morbidity and mortality to newly encountered infections through innate immune training, which can be enhanced by childhood vaccination. Fibroblastic reticular cells (FRCs) are stromal cells in lymphoid organs that support lymphocyte localization and survival and modulate adaptive immune responses. IL-17 signaling is important for FRC metabolism and proliferation during inflammatory responses. Here, we show that FRC-intrinsic IL-17 signaling was required for protective antibody-mediated immunity to the gut bacterial pathogen Citrobacter rodentium. We asked whether prior activation of FRC through nonspecific inflammatory "training" of the gut would alter subsequent immune response to C. rodentium. Inflammatory training increased the number of activated FRC in mesenteric LN (MLN) and enhanced the antibody response to C. rodentium in an IL-17­dependent manner. FRC demonstrated cardinal features of innate immune training, including increased epigenetic markers of activation and increased metabolic response to infection. Enhanced responses were still evident 6 weeks after training. The kinetics of bacterial infection were not changed by inflammatory training, but colon inflammation was paradoxically reduced. Mechanistically, IL-10 production by activated B cells was required for colon protective effects of inflammatory training. Enhancing tissue protective B cell responses thus led to increased production of antibody and IL-10, allowing clearance of infection with reduced tissue inflammation. These data identify a new mode of immune training through FRC to modulate future adaptive responses and better preserve host health.


Subject(s)
B-Lymphocytes/immunology , Fibroblasts/immunology , Immunity, Mucosal/immunology , Interleukin-10/biosynthesis , Interleukin-17/immunology , Animals , Female , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic
11.
Nanoscale Adv ; 4(1): 111-116, 2021 Dec 21.
Article in English | MEDLINE | ID: mdl-36132945

ABSTRACT

The strain effect is a critical knob to tune the catalytic performance and has received unprecedented research interest recently. However, it is difficult to distinguish the strain effect from the synergistic effect, especially in alloyed catalysts. Here we have synthesized Pd@PdAg icosahedra and {111} truncated bi-pyramids with only different surface strains between them as electrocatalysts for the ethanol oxidation reaction (EOR). Due to the same exposed facets and compositions of the two electrocatalysts, their EOR performances are mainly determined by the surface strains of PdAg alloys. These two electrocatalysts provide a perfect model to investigate the role of the strain effect in tuning the EOR performance. It is indicated that Pd@PdAg {111} truncated bi-pyramids with a surface strain of 0.3% show better catalytic activity and durability than Pd@PdAg icosahedra with a surface strain of 2.1% including commercial Pd/C. Density functional theory (DFT) calculations reveal that the lowered d-band center of 0.3% strained PdAg alloys relative to 2.1% strained ones reduced the adsorption energy of the acetate-evolution key intermediate *CH3CO, thereby promoting the enhancement in the catalytic performance of Pd@PdAg nanocrystals for the EOR. Electrochemical analysis further verifies this demonstration on the key role of the strain effect in PdAg alloys for tuning catalytic performance.

12.
RSC Adv ; 11(23): 13848-13852, 2021 Apr 13.
Article in English | MEDLINE | ID: mdl-35423908

ABSTRACT

A simple, and practical oxidative scission of aromatic olefins to carbonyl compounds using O2 as the sole oxidant with poly(ethylene glycol) dimethyl ether as a benign solvent has been developed. A wide range of monosubstituted, gem-disubstituted, 1,2-disubstituted, trisubstituted and tetrasubstituted aromatic olefins was successfully converted into the corresponding aldehydes and ketones in excellent yields even with gram-scale reaction. Some control experiments were also conducted to support a possible reaction pathway.

13.
Bioorg Chem ; 93: 103309, 2019 12.
Article in English | MEDLINE | ID: mdl-31585266

ABSTRACT

The antibacterial agents and therapies today are facing serious problems such as drug resistance. Introducing dual inhibiting effect is a valid approach to solve this trouble and bring advantages including wide adaptability, favorable safety and superiority of combination. We started from potential DNA Gyrase inhibitory backbone isatin to develop oxoindolin derivatives as atypical dual Gyrase (major) and FabH (assistant) inhibitors via a two-round screening. Aiming at blocking both duplication (Gyrase) and survival (FabH), most of synthesized compounds indicated potency against Gyrase and some of them inferred favorable inhibitory effect on FabH. The top hit I18 suggested comparable Gyrase inhibitory activity (IC50 = 0.025 µM) and antibacterial effect with the positive control Novobiocin (IC50 = 0.040 µM). FabH inhibitory activity (IC50 = 5.20 µM) was also successfully introduced. Docking simulation hinted possible important interacted residues and binding patterns for both target proteins. Adequate Structure-Activity Relation discussions provide the future orientations of modification. With high potency, low initial toxicity and dual inhibiting strategy, advanced compounds with therapeutic methods will be developed for clinical application.


Subject(s)
Acetyltransferases/antagonists & inhibitors , DNA Gyrase/chemistry , Escherichia coli Proteins/antagonists & inhibitors , Indoles/chemistry , Topoisomerase II Inhibitors/chemistry , 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase , Acetyltransferases/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Binding Sites , DNA Gyrase/metabolism , Drug Evaluation, Preclinical , Escherichia coli/enzymology , Escherichia coli Proteins/metabolism , Fatty Acid Synthase, Type II/antagonists & inhibitors , Fatty Acid Synthase, Type II/metabolism , Indoles/metabolism , Indoles/pharmacology , Microbial Sensitivity Tests , Molecular Docking Simulation , Protein Structure, Tertiary , Structure-Activity Relationship , Topoisomerase II Inhibitors/metabolism , Topoisomerase II Inhibitors/pharmacology
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 220: 117134, 2019 Sep 05.
Article in English | MEDLINE | ID: mdl-31141780

ABSTRACT

Palladium (Pd) has drawn worldwide attentions because its connections to industry, chemistry, biological material and public health. Quantitative and selective detection tools for Pd and its ion forms are in urgent necessity. Here an umbelliferone derivative Umb-Pd2 was provided as a small, steady, safe and selective sensor for detecting Pd(II). It indicated advantages including sensitive (LOD 1.1 nM), wide pH tolerance (5.0-10.0), applicable linear range (0-1.8 equivalent) and low toxicity. The most attractive point was its explicit selectivity towards Pd(II) from Pd(0) in both independent and coexistence systems. This distinguishing ability was further utilized in imaging in living cells, raising this work as a rare and important example among all the published papers on palladium sensing. Thus, Umb-Pd2 supplied a potential approach for further improvement and applications in both daily chemistry and public health.


Subject(s)
Fluorescent Dyes/chemistry , Palladium/analysis , Spectrometry, Fluorescence/methods , Umbelliferones/chemistry , Animals , Cations/analysis , Cations/chemistry , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/toxicity , HEK293 Cells , HeLa Cells , Humans , Hydrogen-Ion Concentration , Limit of Detection , Magnetic Resonance Spectroscopy , Molecular Imaging/methods , Palladium/chemistry , Palladium/urine , Rats , Sensitivity and Specificity
15.
Eur J Med Chem ; 169: 168-184, 2019 May 01.
Article in English | MEDLINE | ID: mdl-30877972

ABSTRACT

In this paper, 41 hybrid compounds containing diaryl-1,5-diazole and morpholine structures acting as dual COX-2/5-LOX inhibitors have been designed, synthesized and biologically evaluated. Most of them showed potent antiproliferative activities and COX-2/5-LOX inhibitory in vitro. Among them, compound A33 displayed the most potency against cancer cell lines (IC50 = 6.43-10.97 µM for F10, HeLa, A549 and MCF-7 cells), lower toxicity to non-cancer cells than celecoxib (A33: IC50 = 194.01 µM vs.celecoxib: IC50 = 97.87 µM for 293T cells), and excellent inhibitory activities on COX-2 (IC50 = 0.17 µM) and 5-LOX (IC50 = 0.68 µM). Meanwhile, the molecular modeling study was performed to position compound A33 into COX-2 and 5-LOX active sites to determine the probable binding models. Mechanistic studies demonstrated that compound A33 could block cell cycle in G2 phase and subsequently induced apoptosis of F10 cells. Furthermore, compound A33 could significantly inhibit tumor growth in F10-xenograft mouse model, and pharmacokinetic study of compound A33 indicated that it showed better stability in vivo. In general, compound A33 could be a promising candidate for cancer therapy.


Subject(s)
Antineoplastic Agents/pharmacology , Arachidonate 5-Lipoxygenase/metabolism , Azoles/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase 2/metabolism , Lipoxygenase Inhibitors/pharmacology , Morpholines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Azoles/chemical synthesis , Azoles/chemistry , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/chemistry , Dose-Response Relationship, Drug , Drug Design , Drug Screening Assays, Antitumor , HEK293 Cells , Humans , Lipoxygenase Inhibitors/chemical synthesis , Lipoxygenase Inhibitors/chemistry , Models, Molecular , Molecular Structure , Morpholines/chemistry , Structure-Activity Relationship
16.
Chem Pharm Bull (Tokyo) ; 67(2): 125-129, 2019.
Article in English | MEDLINE | ID: mdl-30713272

ABSTRACT

Broadened antibacterial activity was introduced to rhodanine derivatives targeting Mycobacterial tuberculosis enoyl-acyl carrier protein reductase (Mtb InhA) by recruiting feature of xacins to bring DNA Gyrase B inhibitory capability. This is significant for preventing further bacterial injections in the tuberculosis treatment. The most potent compound Cy14 suggested comparable bioactivity (IC50 = 3.18 µM for Mtb InhA; IC50 = 10 nM for DNA Gyrase B) with positive controls. Structure-activity relationship discussion and molecular docking model revealed the significance of rhodanine moiety and derived methoxyl on meta-position, pointing out orientations for future modification.


Subject(s)
Anti-Bacterial Agents , Rhodanine/analogs & derivatives , Acyl Carrier Protein , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Oxidoreductases/antagonists & inhibitors , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/enzymology , Rhodanine/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymology , Structure-Activity Relationship
17.
Org Biomol Chem ; 17(2): 264-267, 2019 01 02.
Article in English | MEDLINE | ID: mdl-30539957

ABSTRACT

A chemoselective 1,2-reduction of cycloalkyl vinyl ketones via asymmetric transfer hydrogenation is described. The reduction proceeded smoothly with a chiral diamine ruthenium complex as a catalyst and a HCOOH-NEt3 azeotrope as both a hydrogen source and solvent under mild conditions. A wide range of 1-cycloalkyl chiral allylic alcohols were obtained in good yields and up to 87% ee. It was found that the alkyl group plays an important role in the enantioselectivity.

18.
Anal Chim Acta ; 1043: 123-131, 2018 Dec 28.
Article in English | MEDLINE | ID: mdl-30392660

ABSTRACT

Pre-clinical diagnosis of many diseases required quantitative detection of Human Serum Albumin (HSA). Herein a high-selective HSA sensor RhHSA was picked through a two-round selectivity evolution from the typical "Effector-π-Trigger" style. RhHSA suggested advantages including high selective (∼6 fold for HSA:BSA = 1:10), sensitive (LOD ∼ 5 nM, over 700-fold enhancement), steady (over 24 h) and wide linear range (0-0.5 mg/mL, applicative for conventional HSA measurement). The detecting system was free from media polarity or viscosity. HSA destruction, site competition and molecular docking provided reliable evidence for the fact that RhHSA could be embedded into both ibuprofen and phenylbutazone sites of HSA. These hints also supported the discrimination of HSA from BSA. Stepwisely fluid replacement in living cells and measuring in urine system both inferred the potential of RhHSA in biological applications.


Subject(s)
Fluorescent Dyes/chemistry , Serum Albumin, Bovine/analysis , Serum Albumin, Human/analysis , Spectrometry, Fluorescence , Animals , Binding Sites , Cattle , Fluorescent Dyes/metabolism , Humans , Limit of Detection , MCF-7 Cells , Microscopy, Fluorescence , Molecular Docking Simulation , Protein Binding , Quantum Theory , Rhodamines/chemistry , Serum Albumin, Bovine/metabolism , Serum Albumin, Human/isolation & purification , Serum Albumin, Human/metabolism
19.
Anal Sci ; 34(12): 1411-1417, 2018 Dec 10.
Article in English | MEDLINE | ID: mdl-30197384

ABSTRACT

A highly selective and sensitive probe, DAC-Hg, has been designed and synthesized for the naked-eye detection of Hg2+ in practical applications. DAC-Hg showed applicative "turn-off" sensing for Hg2+ over other ions. The detection limit was determined to be 5.0 nM, the same as the strictest standard of Hg2+ measurements. A naked-eye evaluation with test strips demonstrated the potential of DAC-Hg for conveniently handled in-situ detection. The application of this established method for analyzing environmental and seafood samples supplied satisfactory results. Therefore, DAC-Hg offered a promising approach for Hg2+ detection as well as hints for sensing other heavy and transition metal ions.


Subject(s)
Colorimetry/methods , Coumarins/chemistry , Environmental Pollutants/analysis , Fluorescent Dyes/chemistry , Mercury/analysis , Spectrometry, Fluorescence/methods , Fluorescent Dyes/chemical synthesis , Limit of Detection , Molecular Structure
20.
Bioorg Med Chem Lett ; 28(19): 3182-3186, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30170940

ABSTRACT

By recruiting the important moiety from Shikonin, a series of novel oxoindoline derivatives S1-S20 have been synthesized for inhibiting H. pylori urease. The most potent compound S18 displayed better activity (IC50 = 0.71 µM; MIC = 0.48 µM) than the positive controls AHA (IC50 = 17.2 µM) and Metronidazole (MIC = 31.3 µM). With low cytotoxicity, it showed considerable potential for further development. Docking simulation revealed the possible binding pattern of this series. 3D QSAR model was built to discuss SAR and give useful hints for future modification.


Subject(s)
Drug Development , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Helicobacter pylori/enzymology , Indoles/chemical synthesis , Indoles/pharmacology , Urease/antagonists & inhibitors , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Computer Simulation , Enzyme Inhibitors/chemistry , Helicobacter pylori/drug effects , Indoles/chemistry , Inhibitory Concentration 50 , Molecular Docking Simulation , Quantitative Structure-Activity Relationship
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