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1.
Sci Rep ; 14(1): 14447, 2024 06 24.
Article in English | MEDLINE | ID: mdl-38914607

ABSTRACT

We examined the joint association of physical activity (PA) and socio-economic status (SES) on all-causes and cardiovascular disease (CVD) mortality in 6945 elderly Koreans (mean age: 71.6 years, 41.8% male) using data from the Korean National Health and Nutrition Examination Survey (2007-2013) and death data from Statistics Korea (2019). The SES included household income and education level. PA was assessed using the IPAQ and categorized according to the 2018 PA Guidelines. In stratified analyses using Cox proportional hazards by SES adherence to PA guidelines those who low household income group was associated with a reduced risk of all-cause mortality and CVD mortality, while in the lowest educational level group, it was associated with a reduced risk of all-cause mortality and CVD mortality. In the joint analysis, PA was associated with a significant reduction in all-cause mortality in all groups when compared with those who did not meet PA those who had the lowest SES. However, PA with CVD mortality risk was not significantly associated in the 'upper-middle' income and 'high school' education groups. The study revealed that PA significantly association mortality, particularly among older adults with low SES. This finding suggests the potential for targeted government interventions to promote healthy aging.


Subject(s)
Cardiovascular Diseases , Exercise , Nutrition Surveys , Social Class , Humans , Male , Aged , Female , Republic of Korea/epidemiology , Retrospective Studies , Cardiovascular Diseases/mortality , Mortality/trends , Aged, 80 and over , Proportional Hazards Models , Socioeconomic Factors , Risk Factors
2.
J Immunother Cancer ; 12(6)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38925680

ABSTRACT

BACKGROUND: The majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S228P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc-Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc-Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks. METHODS: Trastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc-Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S228P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S228P-R409K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populations RESULTS: Experiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc-Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects. CONCLUSIONS: Fc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc-Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S228P-R409K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.


Subject(s)
Immunoglobulin G , Immunotherapy , Immunoglobulin G/immunology , Animals , Mice , Humans , Immunotherapy/methods , Immunoglobulin Fc Fragments/pharmacology , Female , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism
3.
Nat Mater ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937585

ABSTRACT

Organic semiconductors (OSCs) are one of the most promising candidates for flexible, wearable and large-area electronics. However, the development of n-type OSCs has been severely held back due to the poor stability of their most candidates, that is, the intrinsically high reactivity of negatively charged polarons to oxygen and water. Here we demonstrate a general strategy based on vitamin C to stabilize n-type OSCs, remarkably improving the performance and stability of their device, for example, organic field-effect transistors. Vitamin C scavenges reactive oxygen species and inhibits their generation by sacrificial oxidation and non-sacrificial triplet quenching in a cascade process, which not only lastingly prevents molecular structure from oxidation damage but also passivates the latent electron traps to stabilize electron transport. This study presents a way to overcome the long-standing stability problem of n-type OSCs and devices.

4.
Nat Metab ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937659

ABSTRACT

The low-carbohydrate ketogenic diet (KD) has long been practiced for weight loss, but the underlying mechanisms remain elusive. Gut microbiota and metabolites have been suggested to mediate the metabolic changes caused by KD consumption, although the particular gut microbes or metabolites involved are unclear. Here, we show that KD consumption enhances serum levels of taurodeoxycholic acid (TDCA) and tauroursodeoxycholic acid (TUDCA) in mice to decrease body weight and fasting glucose levels. Mechanistically, KD feeding decreases the abundance of a bile salt hydrolase (BSH)-coding gut bacterium, Lactobacillus murinus ASF361. The reduction of L. murinus ASF361 or inhibition of BSH activity increases the circulating levels of TDCA and TUDCA, thereby reducing energy absorption by inhibiting intestinal carbonic anhydrase 1 expression, which leads to weight loss. TDCA and TUDCA treatments have been found to protect against obesity and its complications in multiple mouse models. Additionally, the associations among the abovementioned bile acids, microbial BSH and metabolic traits were consistently observed both in an observational study of healthy human participants (n = 416) and in a low-carbohydrate KD interventional study of participants who were either overweight or with obesity (n = 25). In summary, we uncover a unique host-gut microbiota metabolic interaction mechanism for KD consumption to decrease body weight and fasting glucose levels. Our findings support TDCA and TUDCA as two promising drug candidates for obesity and its complications in addition to a KD.

5.
Chem Sci ; 15(17): 6410-6420, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38699269

ABSTRACT

The application of thermally activated delay fluorescence (TADF) emitters in the orange-red regime usually suffers from the fast non-radiative decay of emissive singlet states (kSNR), leading to low emitting efficiency in corresponding organic light-emitting diode (OLED) devices. Although kSNR has been quantitatively described by energy gap law, how ultrafast molecular motions are associated with the kSNR of TADF emitters remains largely unknown, which limits the development of new strategies for improving the emitting efficiency of corresponding OLED devices. In this work, we employed two commercial TADF emitters (TDBA-Ac and PzTDBA) as a model system and attempted to clarify the relationship between ultrafast excited-state structural relaxation (ES-SR) and kSNR. Spectroscopic and theoretical investigations indicated that S1/S0 ES-SR is directly associated with promoting vibrational modes, which are considerably involved in electronic-vibrational coupling through the Huang-Rhys factor, while kSNR is largely affected by the reorganization energy of the promoting modes. By restraining S1/S0 ES-SR in doping films, the kSNR of TADF emitters can be greatly reduced, resulting in high emitting efficiency. Therefore, by establishing the connection among S1/S0 ES-SR, promoting modes and kSNR of TADF emitters, our work clarified the key role of external structural restraint for achieving high emitting efficiency in TADF-based OLED devices.

6.
Pain ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38787639

ABSTRACT

ABSTRACT: The profiles of muscle and joint pain throughout the menopausal transition and the factors associated with these symptoms have not been determined. A total of 609 participants from a longitudinal cohort study conducted in an urban Chinese community were enrolled in this study. We assessed the prevalence of musculoskeletal symptoms at different menopausal stages and explored the factors associated with these symptoms. The prevalence and severity of muscle and joint pain increase as menopausal stages progress, and late menopausal transition may be a crucial timepoint that triggers the onset of musculoskeletal pain. The results of the multivariate analysis revealed that poor health status (OR = 2.245, 95% CI = 1.714-2.94, P < 0.001), body mass index (BMI) (OR = 1.046, 95% CI = 1.01-1.084, P = 0.011), the presence of anxiety (OR = 1.601, 95% CI = 1.211-2.117, P < 0.001), and depression (OR = 1.368, 95% CI = 1.143-1.639, P < 0.001) were independently associated with muscle and joint pain. In addition, the severity of musculoskeletal pain was related to poor health status (OR = 2.738, 95% CI = 1.91-3.924, P < 0.001) and depression (OR = 1.371, 95% CI = 1.095-1.718, P = 0.006). Musculoskeletal symptoms are frequent somatic symptoms experienced by Chinese middle-aged women. Women with poor health status, high BMI, anxiety, and depression were at heightened risk of experiencing musculoskeletal pain. The severity of pain increased over time.

7.
Med ; 5(6): 622-644.e8, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38663402

ABSTRACT

BACKGROUND: Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders. METHODS: By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO) mouse stroke model, we examined the effects and underlying mechanisms of genetic and pharmacological inhibition of the cGAS-STING pathway on long-term post-stroke neurological functional outcomes. FINDINGS: Blocking the cGAS-STING pathway, even 3 days after tMCAO, significantly promoted functional recovery in terms of white matter structural and functional integrity as well as sensorimotor and cognitive functions. Mechanistically, the neuroprotective effects via inhibiting the cGAS-STING pathway were contributed not only by inflammation repression at the early stage of tMCAO but also by modifying the cell state of phagocytes to facilitate remyelination at the sub-acute phase. The activation of the cGAS-STING pathway significantly impeded post-stroke remyelination through restraining myelin debris uptake and degradation and hindering oligodendrocyte differentiation and maturation. CONCLUSIONS: Manipulating the cGAS-STING pathway has an extended treatment window in promoting long-term post-stroke functional recovery via facilitating remyelination in a mouse stroke model. Our results highlight the roles of the cGAS-STING pathway in aggregating stroke pathology and propose a new way for improving functional recovery after ischemic stroke. FUNDING: This work was primarily funded by the National Key R&D Program of China.


Subject(s)
Disease Models, Animal , Membrane Proteins , Nucleotidyltransferases , Recovery of Function , Remyelination , Animals , Nucleotidyltransferases/metabolism , Nucleotidyltransferases/genetics , Membrane Proteins/metabolism , Membrane Proteins/genetics , Mice , Recovery of Function/drug effects , Remyelination/drug effects , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Signal Transduction/drug effects , Male , Mice, Inbred C57BL , Stroke/drug therapy , Stroke/metabolism , Ischemic Stroke/drug therapy , Ischemic Stroke/metabolism
8.
Chemistry ; 30(34): e202400046, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38619364

ABSTRACT

Förster resonance energy transfer (FRET) has been widely applied in fluorescence imaging, sensing and so on, while developing useful strategy of boosting FRET efficiency becomes a key issue that limits the application. Except optimizing spectral properties, promoting orientation factor (κ2) has been well discussed but rarely utilized for boosting FRET. Herein, we constructed binary nano-assembling of two thermally activated delayed fluorescence (TADF) emitters (2CzPN and DMAC-DPS) with J-type aggregate of cyanine dye (C8S4) as doping films by taking advantage of their electrostatic interactions. Time-resolved spectroscopic measurements indicated that 2CzPN/Cy-J films exhibit an order of magnitude higher kFRET than DMAC-DPS/Cy-J films. Further quantitative analysing on kFRET and kDET indicated higher orientation factor (κ2) in 2CzPN/Cy-J films play a key role for achieving fast kFRET, which was subsequently confirmed by anisotropic measurements. Corresponding DFT/TDDFT calculation revealed strong "two-point" electrostatic anchoring in 2CzPN/Cy-J films that is responsible for highly orientated transitions. We provide a new strategy for boosting FRET in nano-assemblies, which might be inspired for designing FRET-based devices of sensing, imaging and information encryption.

9.
Anal Chem ; 96(16): 6356-6365, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38588440

ABSTRACT

Renal fibrosis poses a significant threat to individuals suffering from chronic progressive kidney disease. Given the absence of effective medications for treating renal fibrosis, it becomes crucial to assess the extent of fibrosis in real time and explore the development of novel drugs with substantial therapeutic benefits. Due to the accumulation of renal tissue damage and the uncontrolled deposition of fibrotic matrix during the course of the disease, there is an increase in viscosity both intracellularly and extracellularly. Therefore, a viscosity-sensitive near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging probe, BDP-KY, was developed to detect aberrant changes in viscosity during fibrosis. Furthermore, BDP-KY has been applied to screen the effective components of herbal medicine, rhubarb, resulting in the identification of potential antirenal fibrotic compounds such as emodin-8-glucoside and chrysophanol 8-O-glucoside. Ultrasound, PA, and NIRF imaging of a unilateral uretera obstruction mice model show that different concentrations of emodin-8-glucoside and chrysophanol 8-O-glucoside effectively reduce viscosity levels during the renal fibrosis process. The histological results showed a significant decrease in fibrosis factors α-smooth muscle actin and collagen deposition. Combining these findings with their pharmacokinetic characteristics, these compounds have the potential to fill the current market gap for effective antirenal fibrosis drugs. This study demonstrates the potential of BDP-KY in the evaluation of renal fibrosis, and the two identified active components from rhubarb hold great promise for the treatment of renal fibrosis.

10.
Biol Reprod ; 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38320203

ABSTRACT

Accumulating evidence indicates that paternally-derived miRNAs play a crucial role in the development of early embryos and are regarded as the key factor in the successful development of somatic cell cloned embryos. In our previous study, bta-miR-301a was found to be highly expressed in bovine sperm, and was delivered into oocytes during fertilization. In this study, bioinformatics, dual luciferase reporter assays, rescue experiments and gain- and loss-of-function experiments indicated that ACVR1 is the target gene of bta-miR-301a in early bovine embryos. By microinjecting bta-miR-301a mimic into embryos of parthenogenetic or somatic cell nuclear transfer, we observed that bta-miR-301a prolonged the first cleavage time of the embryos and increased the blastocyst formation rate. Thus, this study provides preliminary evidence that bta-miR-301a influences remodeling of the microfilament skeleton, prolongs the first cleavage time, and improves the developmental competence of embryos by negatively regulating ACVR1 translation.

11.
J Cancer ; 15(4): 1041-1052, 2024.
Article in English | MEDLINE | ID: mdl-38230224

ABSTRACT

Background: Dopamine receptors have been reported to be involved in pain, while the exact effects and mechanism in bone cancer pain have not been fully explored. Methods: Bone cancer pain model was created by implanting walker 256 mammary gland carcinoma into right tibia bone cavity. Primary cultured spinal neurons were used for in vitro evaluation. FLIPR, western-blot, immunofluorescence, and Co-IP were used to detect cell signaling pathway. Results: Our results indicated that spinal dopamine D1 receptor (D1DR) and spinal dopamine D2 receptor (D2DR) could form heteromers in TCI rats, and antagonizing spinal D1DR and D2DR reduced heteromers formation and alleviated TCI-induced bone cancer pain. Further results indicated that D1DR or D2DR antagonist induced antinociception in TCI rats could be reversed by D1DR, D2DR, and D1/D2DR heteromer agonists. And Gq, IP3, and PLC inhibitors also attenuated TCI-induced bone cancer pain. In vitro results indicated that D1DR or D2DR antagonist decreased the Ca2+ oscillations upregulated by D1DR, D2DR, and D1/D2DR heteromer agonists in activated primary cultured spinal neurons. Moreover, inhibition of D1/D2DR heteromers induced antinociception in TCI rats was partially mediated by the CaMKII and MAPKs pathway. In addition, a natural compound levo-Corydalmine (l-CDL), could inhibit D1/D2DR heteromers and attenuate bone cancer pain. Results: Inhibition of spinal D1/D2DR heteromers via l-CDL decreases excitability in spinal neurons, which might present new therapeutic strategy for bone cancer pain.

12.
Environ Sci Pollut Res Int ; 31(5): 7146-7166, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38157182

ABSTRACT

China has implemented a series of environmental policies aimed at promoting green and innovative development by enterprises, to mitigate the adverse effects of environmental pollution. However, the frequent revision and introduction of environmental policies have also increased enterprises' perception of environmental uncertainty. This study, based on the upper echelon theory, uses data from listed companies in China from 2011 to 2021 to construct an index of perceived environmental uncertainty of firms through textual analysis and empirically examines its impact on green innovation and its potential mechanisms and boundary effects. The results show that, first, perceived environmental uncertainty of firms has a noteworthy inhibiting impact on green innovation. Second, mechanism analysis reveals that perceived environmental uncertainty of firms inhibits green innovation mainly in two ways: reducing the level of transparency in corporate information and reducing R&D investment. Third, the moderating effect finds that government subsidies can mitigate the inhibitory impact of perceived environmental uncertainty on green innovation among firms. In other words, higher government subsidies correspond to a reduced inhibitory effect of perceived environmental uncertainty on green innovation among firms. In addition, heterogeneity analysis shows that this inhibition is more obvious in non-state-owned enterprises, small enterprises, and enterprises in non-heavy pollution industries. This study holds immense practical significance for enterprises in harnessing the opportunities of green innovation amidst perceived environmental uncertainty, facilitating progressive green development, and ultimately fostering the harmonized growth of economic and environmental benefits for enterprises.


Subject(s)
Environmental Policy , Sustainable Development , Humans , China , Uncertainty
13.
Drug Deliv Transl Res ; 14(7): 1820-1838, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38127247

ABSTRACT

Uric acid is the final metabolite in humans. High level of uric acid chronically induces urate deposition, aggravates kidney damage, and concomitantly causes an increase in inflammatory factors. Alleviating acute inflammation and decreasing uric acid levels are the key points in the treatment of inflammatory diseases associated with high uric acid. However, a drug delivery system that combines anti-inflammatory and uric acid reduction functions at the same time remains a challenge to be settled. Here, we designed a nanocrystal-based co-delivery platform, IND Nplex, characterized by loading of indomethacin (IND) and uricase. Compared with free IND or uricase, IND Nplex possessed a better anti-inflammatory effect by restraining the release of inflammation-related factors in vitro. In addition, pharmacokinetic and biodistribution studies revealed that IND Nplex significantly prolonged the retention time in vivo and was more concentrated in the kidney. In acute gouty arthritis model rats, IND Nplex markedly relieved ankle joint swelling and mitigated synovial inflammation. In acute kidney injury model rats, IND Nplex indicated better biocompatibility and significant amelioration of renal fibrosis. Moreover, IND Nplex showed the effect of anti-inflammatory and improved renal function via determination of inflammatory factors and biochemical markers in the serum and kidney. In conclusion, these results indicate that IND Nplex exerts anti-inflammatory activity and uric acid-lowering effect and could become a promising candidate for the treatment of uric acid-related diseases.


Subject(s)
Arthritis, Gouty , Indomethacin , Rats, Sprague-Dawley , Urate Oxidase , Uric Acid , Indomethacin/administration & dosage , Animals , Urate Oxidase/administration & dosage , Urate Oxidase/pharmacokinetics , Urate Oxidase/therapeutic use , Uric Acid/blood , Male , Arthritis, Gouty/drug therapy , Nanoparticles/administration & dosage , Rats , Mice , Inflammation/drug therapy , Tissue Distribution , Acute Kidney Injury/drug therapy , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Drug Delivery Systems , Kidney/drug effects , Kidney/metabolism , Humans , RAW 264.7 Cells , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/pharmacology
14.
Nano Lett ; 24(1): 472-478, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38146703

ABSTRACT

Strain engineering has been used as an efficient method to modulate various properties of quantum materials and electronic devices. One may establish piezo effects based on a disciplined response to the strain in multifunctional nanosystems. Inspired by a recent theoretical proposal on the interesting piezomagnetism and C-paired valley polarization in the V2Se2O monolayer, we predict a stable altermagnetic Janus monolayer V2SeTeO using density functional theory calculations. It exhibits a novel "multipiezo" effect combining piezoelectricity, piezovalley, and piezomagnetism. Most interestingly, the valley polarization and the net magnetization under strain in V2SeTeO exceed these in V2Se2O, along with the additional large piezoelectric coefficient. The "multipiezo" effect makes Janus monolayer V2SeTeO as a tantalizing material for potential applications in nanoelectronics, optoelectronics, spintronics, and valleytronics.

15.
Adv Sci (Weinh) ; 10(33): e2303926, 2023 11.
Article in English | MEDLINE | ID: mdl-37870188

ABSTRACT

The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high-throughput screening (HTS) of natural protectants, and elucidating the molecular mechanism of intervention in AKI. Herein, the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI is reported. CDIA has near-infrared fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 h using this probe is superior to the 48-hour detection time for typical clinical assays, such as blood urea nitrogen and serum creatinine detection. Furthermore, a method is established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin is screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual-mode tool for illuminating the •OH-related pathological process in AKI and screening additional compounds to prevent and treat AKI.


Subject(s)
Acute Kidney Injury , Fluorescent Dyes , Humans , Hydroxyl Radical/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , High-Throughput Screening Assays , Lighting , NF-E2-Related Factor 2/metabolism , Acute Kidney Injury/diagnosis , Acute Kidney Injury/metabolism , Kidney/metabolism
16.
J Phys Chem Lett ; 14(43): 9665-9676, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37870971

ABSTRACT

The emerging nitrogen-embedded multiple resonance (MR) emitters with an indolo[3,2,1-jk] carbazole (ICz) unit have exhibited promising performance for high-resolution organic light-emitting diode (OLED) devices, while the underlying photophysics has been rarely reported. In this work, the optical spectra, color purity, and emitting efficiency of ICz-based MR emitters were investigated by using electronic structure and thermal vibration correlation function (TVCF) calculations. Unlike B-N MR emitters, the high color purity of investigated ICz-based MR emitters was mainly contributed by considerable structural rigidity, which also greatly affects the radiative decay rate and fluorescence quantum yield of the S1 state. For the majority of investigated emitters, potential reverse intersystem crossing (RISC) channels (T1 → S1 and T2 → S1) are limited by thermally inaccessible ΔEST* or insufficient spin-orbital coupling (SOC), which can be distinguished by the calculated temperature-dependent RISC rate pattern. We provided a systematic photophysical picture for ICz-based MR emitters that might be interesting for the OLED design and application community.

17.
Molecules ; 28(18)2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37764334

ABSTRACT

The emergence of multidrug-resistant bacteria has severely increased the burden on the global health system, and such pathogenic infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly attracting great interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin-secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a 'shotgun' cloning strategy. The chemically synthesized peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed lower salt sensitivity and more rapid bacteria killing compared to SS1. Both peptides employed a membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues against lung cancer cell lines was found to be significant.


Subject(s)
Antimicrobial Peptides , Tarsiidae , Humans , Animals , Anura , Skin , Escherichia coli
18.
Oncol Lett ; 26(4): 460, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37745980

ABSTRACT

The tumor microenvironment (TME) and Warburg effect are critical for the regulation of tumor metastasis. The monocarboxylate transporter (MCT) family members, particularly MCT4, which is encoded by the solute carrier family 16 member 3 gene, play an important role in the regulation of the TME and mediation of the Warburg effect by transporting lactate out of cancer cells. Migration and invasion are two key features of metastasis. Few studies have investigated the mechanism by which MCT4 promotes cell migration, and the suggested mechanisms by which MCT4 promotes migration vary in different tumor cell models. The purpose of the present study was to use non-cancerous cells as a research model to investigate the specific mechanism underlying the promotion of migration by MCT4. In a previous study, murine L929 cells overexpressing human MCT4 (MCT4-L929 cells) were generated and MCT4 was demonstrated to promote the migration and invasion of these non-cancerous cells. In the present study, MCT4-L929 cells and control-L929 cells were used to investigate the potential pathways and mechanisms through which MCT4 promotes cell migration. RNA sequencing analysis revealed 872 differentially expressed genes, comprising 337 and 535 upregulated and downregulated genes, respectively, in the MCT4-L929 cells. Reverse transcription-quantitative analysis and western blotting revealed that MCT4 overexpression increased the transcription and protein levels of insulin-like growth factor 1 (IGF1). In a wound healing assay, the migration of exogenous mouse IGF1-treated control-L929 cells was similar to that of MCT4-L929 cells. Additionally, the inhibition of IGF1 receptor (IGF1R) or serum/glucocorticoid regulated kinase 1 (SGK1), a downstream protein in the IGF1 and phosphoinositide 3-kinase PI3K regulatory subunit 3 (PIK3R3) pathways, in MCT4-L929 cells mitigated the cell migration-promoting effect of MCT4. These novel findings suggest that MCT4 may promote the migration of L929 fibroblast cells via activation of the IGF1/IGF1R/PIK3R3/SGK1 axis.

19.
World J Surg Oncol ; 21(1): 273, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37644549

ABSTRACT

BACKGROUND: Using grip strength as a predictor of nutritional risk and early ambulation for gastrointestinal tumor surgery and determining its critical value have not been reported. This study was designed to explore the influencing factors of early postoperative ambulation ability for patients with gastrointestinal tumors who underwent laparoscopic surgery. METHODS: Four-hundred twenty-seven patients with gastrointestinal tumors who underwent laparoscopic surgery at three tertiary A hospitals in Beijing were prospectively enrolled. Subsequently, logistic regression analysis was conducted to determine the independent predictors of early postoperative ambulation. Logistic regression analyses for the different gender were also performed. In addition, the effectiveness of preoperative grip strength measurement in nutritional risk assessment was analyzed by using nutritional risk score 2002 (NRS 2002) as a control. RESULTS: The included cases were comprised of 283 male and 144 female patients, with an age of 59.35 ± 11.70 years. Gender, preoperative grip strength, operative time, and number of indwelling tubes were independent predictors of early postoperative ambulation. In the male group, lower preoperative grip strength and more indwelling tubes were independent risk factors for early postoperative ambulation. In the female group, lower preoperative grip strength and extended operating time were independent risk factors. Moreover, preoperative grip strength (male < 32 kg, female < 21 kg) can be used as a risk predictor for both preoperative nutritional risk and early postoperative ambulation. CONCLUSIONS: As a simple and objective measure of muscle strength, grip strength measurement is expected to be an effective predictor for both early postoperative ambulation ability and nutritional status of patients.


Subject(s)
Gastrointestinal Neoplasms , Laparoscopy , Humans , Female , Male , Middle Aged , Aged , Early Ambulation , Prospective Studies , Gastrointestinal Neoplasms/surgery , Hand Strength , Laparoscopy/adverse effects
20.
Chem Biodivers ; 20(9): e202300556, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37469185

ABSTRACT

In this article, two undescribed amides (1-2) with an unusual (2-formyl-5-hydroxymethyl)pyrroyl-butylamine moiety were obtained from the Physochlainae Radix. Comprehensive spectroscopic studies, including NMR and HR-ESI-MS, coupling with spectroscopic data comparisons were used to determine structures. Anti-inflammatory assay results showed that new amides possessed significant inhibitory activities of the NO production of LPS-induced RAW 264.7 cells, with IC50 values of 17.52±1.68 µM and 20.37±2.42 µM, respectively.


Subject(s)
Amides , Anti-Inflammatory Agents , Animals , Mice , Amides/pharmacology , Anti-Inflammatory Agents/pharmacology , RAW 264.7 Cells , Molecular Structure
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