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1.
Clin Ophthalmol ; 18: 1879-1888, 2024.
Article in English | MEDLINE | ID: mdl-38952720

ABSTRACT

Purpose: To evaluate the effectiveness of Zhang and Zheng's InnovEyes (ZZ InnovEyes) strategy for optimizing outcomes of ray-tracing-guided laser in situ keratomileusis (LASIK) compared to the standard automated strategy. Methods: A total of 38 patients (71 eyes) undergoing therapeutic refractive surgery at Hangzhou MSK Eye Hospital were randomly assigned to the ZZ InnovEyes and automated groups using double-masked randomization. The study assessed visual acuity, refractive outcomes, and higher-order aberrations preoperatively and at 1-day, 2-week, 1-month, and 3-month follow-ups. Statistical analysis was done with Microsoft Excel and SPSS 19.0. Results: The exposure and control groups comprised 36 and 35 eyes, respectively. The ZZ InnovEyes group demonstrated significant advantages in manifest refraction spherical equivalent (MRSE) correction compared to the automated approach group (0.13 ± 0.30 D vs 0.62 ± 0.40 D, p < 0.001), achieving 97.22% uncorrected distance visual acuity (UDVA) of 20/16 or better compared to 85.71% in the automated group at the 3-month follow-up (p = 0.08), and achieving 50.00% UDVA of 20/12.5 or better compared to 28.57% in the automated group at the 3-month follow-up (p = 0.06). Loss lines from preoperative corrected distance visual acuity to postoperative UDVA were lower in the ZZ InnovEyes group (0.00%) than the automated group (8.57%; p = 0.07). Both groups exhibited similar astigmatism corrections and higher-order aberrations. Conclusion: The ZZ InnovEyes strategy, which incorporates manifest and wavefront refraction for ray-tracing-guided LASIK, demonstrated superior MRSE correction and potential advantages in visual acuity outcomes compared to the standard automated strategy. This study highlights the need for ongoing optimization and research in refractive surgery. Clinical Trial Registration Number: ChiCTR2300078709.

2.
Arch Virol ; 169(8): 161, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981885

ABSTRACT

Here, we report a novel ourmia-like mycovirus, named "Phomopsis asparagi magoulivirus 1" (PaMV1), derived from the phytopathogenic fungus Phomopsis asparagi. The genome of PaMV1 consists of a positive-sense single-stranded RNA (+ ssRNA) that is 2,639 nucleotides in length, with a GC content of 57.13%. It contains a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) consisting of 686 amino acids with a molecular mass of 78.57 kDa. Phylogenetic analysis based on RdRp sequences revealed that PaMV1 grouped together with Diaporthe gulyae magoulivirus 1 (DgMV1) in a distinct clade. Sequence comparisons and phylogenetic analysis suggest that PaMV1 is a novel member of the genus Magoulivirus, family Botourmiaviridae.


Subject(s)
Fungal Viruses , Genome, Viral , Open Reading Frames , Phomopsis , Phylogeny , RNA, Viral , Fungal Viruses/genetics , Fungal Viruses/classification , Fungal Viruses/isolation & purification , Phomopsis/virology , RNA, Viral/genetics , Whole Genome Sequencing , RNA-Dependent RNA Polymerase/genetics , Base Composition , Plant Diseases/microbiology , Plant Diseases/virology , Viral Proteins/genetics , Base Sequence , RNA Viruses/genetics , RNA Viruses/isolation & purification , RNA Viruses/classification
3.
PLoS One ; 19(7): e0304252, 2024.
Article in English | MEDLINE | ID: mdl-39008455

ABSTRACT

This study explores the peer and economic effects of corporate poverty alleviation behavior. Using the data of A-share non-financial listed corporates in Shanghai and Shenzhen of China from 2016 to 2020, the empirical analysis of this study finds that: corporate poverty alleviation behavior has significant peer effects; the guidance of local poverty alleviation policies weakens the peer effects of corporate poverty alleviation behavior; compared to private enterprises, the poverty alleviation behavior of the peer firms has a more significant impact on state-owned enterprises; and corporate poverty alleviation behavior can result in the backflow of economic benefits and achieve the organic unity of economic and social benefits. The purpose of this paper is to explore the peer effects of corporate poverty alleviation behaviors through empirical analysis using available public data. The results of the study not only increase the motivation of corporate to participate in poverty alleviation from a peer effects perspective, but also reveal key factors for sustaining corporate poverty alleviation behaviors.


Subject(s)
Poverty , China , Humans , Private Sector/economics , Peer Group
4.
Chem Sci ; 15(26): 10214-10220, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38966364

ABSTRACT

Selective recognition and enrichment of fullerenes (e.g., C60 and C70) remains challenging due to the same diameter and geometrical similarity. Herein, we report a hexagonal anthracene-based nanotube (1) through a one-pot Suzuki-Miyaura cross-coupling reaction. With anthracene-based side walls and pyridine linkers, 1 features a nano-scale tubular cavity measuring 1.2 nm in diameter and 0.9 nm in depth, along with pH-responsive properties. Interestingly, the electron-rich 1 shows high binding affinity (K a ≈ 106 M-1) and selectivity (K s ≈ 140) to C70 over C60 in toluene, resulting from their different contribution of π-π interactions with the host. The protonation of 1 simultaneously alters the electronic properties within the nanotube, resulting in the release of the fullerene guests. Lastly, the selective recognition and pH stimuli-responsive properties of the nanotube have been utilized to enrich C70 from its low-content mixtures of fullerenes in chloroform.

5.
J Environ Sci (China) ; 146: 176-185, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38969446

ABSTRACT

Microplastics (MPs) are commonly found with hydrophobic contaminants in the water column and pose a serious threat to aquatic organisms. The effects of polystyrene microplastics of different particle sizes on the accumulation of triclosan in the gut of Xenopus tropicalis, its toxic effects, and the transmission of resistance genes were evaluated. The results showed that co-exposure to polystyrene (PS-MPs) adsorbed with triclosan (TCS) caused the accumulation of triclosan in the intestine with the following accumulation capacity: TCS + 5 µm PS group > TCS group > TCS + 20 µm PS group > TCS + 0.1 µm PS group. All experimental groups showed increased intestinal inflammation and antioxidant enzyme activity after 28 days of exposure to PS-MPs and TCS of different particle sizes. The TCS + 20 µm PS group exhibited the highest upregulated expression of pro-inflammatory factors (IL-10, IL-1ß). The TCS + 20 µm group showed the highest increase in enzyme activity compared to the control group. PS-MPs and TCS, either alone or together, altered the composition of the intestinal microbial community. In addition, the presence of more antibiotic resistance genes than triclosan resistance genes significantly increased the expression of tetracycline resistance and sulfonamide resistance genes, which may be associated with the development of intestinal inflammation and oxidative stress. This study refines the aquatic ecotoxicity assessment of TCS adsorbed by MPs and provides informative information for the management and control of microplastics and non-antibiotic bacterial inhibitors.


Subject(s)
Microplastics , Particle Size , Polystyrenes , Triclosan , Water Pollutants, Chemical , Xenopus , Animals , Triclosan/toxicity , Polystyrenes/toxicity , Water Pollutants, Chemical/toxicity , Microplastics/toxicity , Intestines/drug effects , Adsorption , Gene Expression/drug effects
6.
Chem Commun (Camb) ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973675

ABSTRACT

The solvothermal reaction of CuSO4·5H2O and a chiral R-pempH2 ligand (molar ratio 6 : 1) first forms the metastable intermediate [Cu24(OH)20(R-pempH)8(SO4)10(H2O)10.5]·35H2O (1), followed by the formation of the stable phase [Cu2(OH)(R-pempH)(SO4)(H2O)]·H2O (2). Compound 1 displays a novel 3D open-framework structure containing Cu12 cluster nodes and sulfate links, which can be converted to the layered compound 2. We also investigated the photothermal effects of both compounds.

7.
J Geriatr Cardiol ; 21(6): 651-657, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38973824

ABSTRACT

BACKGROUND: Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce. METHODS: This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed. RESULTS: After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype (P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure (n = 6, 16.7%), followed by mixed (n = 26, 30.6%) and vasodepressive (n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve (P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type (P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC ≥ 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02). CONCLUSIONS: Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC ≥ 8.4 ms might benefit from CNA.

8.
Psychol Res Behav Manag ; 17: 2557-2571, 2024.
Article in English | MEDLINE | ID: mdl-38973976

ABSTRACT

Introduction: People are generally characterized by a self-serving bias which describes the tendency to ascribe positive outcomes or success to internal or personal causes (self-enhancement motivation) and ascribe negative outcomes or failure to external or situational causes (self-protection motivation). It has been found that the individuals with internet gaming disorder (IGD) who have low self-esteem and high depression exhibit an attenuated self-serving bias. However, the relationships among self-esteem, depression and self-serving bias are not clearly identified. Methods: A sample of 138 IGD participants completed self-esteem and depression scales and a causal attribution task (Study 1) to examine the relationships among self-esteem, depression and self-serving bias (both self-enhancement and self-protection). In follow-up Study 2, 28 IGD participants were recruited to undertake self-affirmation intervention which can affirm one's sense of global self-view and bolster self-esteem to explore whether self-affirmation would trigger a reduction of depression and a raise of self-serving bias. Results: The results of path analysis in Study 1 showed that the self-serving bias was predicted by self-esteem and depression, and the depression played a mediating role between self-esteem and self-serving bias. The results of Study 2 showed that the IGD participants reported higher self-esteem, lower depression and engaged in more self-protection motivation after affirming-self manipulation as compared with affirming-other manipulation. Conclusion: These findings suggest that self-esteem predicts self-serving bias through depression and self-affirmation could trigger an increase of self-esteem, further decrease depression and improve self-serving bias for the individuals with IGD. The present article clearly identified the relationships among these factors and provided a new approach to promote positive self-concept in individuals with IGD. Future research is warranted to explore the lasting benefits of self-affirmation on domains of education, relationships and gaming withdrawal for the individuals with IGD among different populations.

9.
Asian J Androl ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39028624

ABSTRACT

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.

10.
Cancer Med ; 13(14): e7435, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39031941

ABSTRACT

OBJECTIVE: TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first-in-human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM). METHODS: This is a multicenter phase I clinical trial consisting of the 3+3 dose-escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28-day cycle. RESULTS: Twenty-five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose-limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any-grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time-to-plasma peak concentration of 0.8-1.5 h. The mean half-life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response-evaluable patients, 63.7% achieved stable disease or better. CONCLUSIONS: TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose-expansion phase.


Subject(s)
Multiple Myeloma , Proteasome Inhibitors , Humans , Multiple Myeloma/drug therapy , Multiple Myeloma/pathology , Male , Middle Aged , Female , Aged , Proteasome Inhibitors/therapeutic use , Proteasome Inhibitors/pharmacokinetics , Proteasome Inhibitors/adverse effects , Proteasome Inhibitors/administration & dosage , Administration, Oral , Maximum Tolerated Dose , Treatment Outcome , Neoplasm Recurrence, Local/drug therapy , Adult , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm
11.
BMC Nurs ; 23(1): 392, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849821

ABSTRACT

AIM: To explore the views and experiences of formal caregivers caring for older inpatients with physical disabilities. METHODS: It was a qualitative phenomenological study. Using purposive sampling, twelve formal caregivers were chosen in a tertiary comprehensive hospital in Hangzhou, China. Semi-structured, face-to-face interviews were conducted, guided by open-ended questions that focused on gaining rich insights into participants' views and experiences. Coding reliability thematic analysis was used to guide data analysis and categorize, based on Lazarus and Folkman's theory of transactional coping. RESULTS: Four themes emerged from the data analysis: (1) Caregiving Threats. (2) motivations. (3) Responsibility Management. (4) Fear. CONCLUSION: Despite facing significant pressure at work, formal caregivers of elderly inpatients with physical disabilities possess the drive and various coping strategies to excel in their role. Identifying caregivers' experiences of care can be helpful in improving resilience to stress and maintaining stability in formal caregivers.

12.
Opt Express ; 32(8): 13851-13863, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859344

ABSTRACT

This paper introduces an innovative, compact, and high-gain metasurface antenna, covering both the 24 GHz millimeter wave (mmWave) radar band and the 5 G n257 and n258 bands. The proposed metasurface antenna consists of a wideband stacked patch antenna and a dual-layer metasurface to focus its radiation beams for multiple mmWave bands. The operating frequency can be slightly shifted by altering the distance between the feeder and the metasurface. The distribution of the metasurface unit cells is designed based on a simplified phase compensation formula. The dimension of the fabricated feeder is 6 mm × 6 mm, and the metasurface occupies a 65 mm × 65 mm radome area. Experimental results demonstrate a wide bandwidth from 23.5 GHz to 29.1 GHz for the feeder, and impressive maximum gains of 19.7 dBi and 19.5 dBi for the lower band and higher band of the metasurface antenna are achieved simultaneously. The frequency reconfiguration ability was characterized by a 750 MHz frequency shift with every 1 mm distance adjustment. The compact size and high gain performance of the proposed design underscore its potential for practical applications in millimeter wave joint communication and radar sensing systems.

13.
Food Chem X ; 22: 101491, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38840727

ABSTRACT

Maillard reaction products (MRPs) derived from rice protein isolate hydrolysate and D-xylose, with or without L-cysteine, were developed as a potential meat flavoring. The combined impact of temperature (80-140 °C) and cysteine on fundamental physicochemical characteristics, antioxidant activity, and flavor of MRPs were investigated through assessments of pH, color, UV-visible spectra, fluorescence spectra, free amino acids, volatile compounds, E-nose, E-tongue, and sensory evaluation. Results suggested that increasing temperature would reduce pH, deepen color, promote volatile compounds formation, and reduce the overall umami and bitterness. Cysteine addition contributed to the color inhibition, enhancement of DPPH radical-scavenging activity and reducing power, improvement in mouthfulness and continuity, reduction of bitterness, and the formation of sulfur compounds responsible for meaty flavor. Overall, MRPs prepared at 120 °C with cysteine addition could be utilized as a potential meat flavoring with the highest antioxidant activity and relatively high mouthfulness, continuity, umami, meaty aroma, and relatively low bitterness.

14.
BMC Plant Biol ; 24(1): 524, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38853253

ABSTRACT

BACKGROUND: Amylose, a prebiotic found in yams is known to be beneficial for the gut microflora and is particularly advantageous for diabetic patients' diet. However, the genetic machinery underlying amylose production remains elusive. A comprehensive characterization of the genetic basis of amylose content in yam tubers is a prerequisite for accelerating the genetic engineering of yams with respect to amylose content variation. RESULTS: To uncover the genetic variants underlying variation in amylose content, we evaluated amylose content in freshly harvested tubers from 150 accessions of Dioscorea zingibensis. With 30,000 high-quality single nucleotide polymorphisms (SNP), we performed a genome-wide association analysis (GWAS). The population structure analysis classified the D. zingiberensis accessions into three groups. A total of 115 significant loci were detected on four chromosomes. Of these, 112 significant SNPs (log10(p) = 5, q-value < 0.004) were clustered in a narrow window on the chromosome 6 (chr6). The peak SNP at the position 75,609,202 on chr6 could explain 63.15% of amylose variation in the population and fell into the first exon of the ADP-glucose pyrophosphorylase (AGPase) small subunit gene, causing a non-synonymous modification of the resulting protein sequence. Allele segregation analysis showed that accessions with the rare G allele had a higher amylose content than those harboring the common A allele. However, AGPase, a key enzyme precursor of amylose biosynthesis, was not expressed differentially between accessions with A and G alleles. Overexpression of the two variants of AGPase in Arabidopsis thaliana resulted in a significantly higher amylose content in lines transformed with the AGPase-G allele. CONCLUSIONS: Overall, this study showed that a major genetic variant in AGPase probably enhances the enzyme activity leading to high amylose content in D. zingiberensis tuber. The results provide valuable insights for the development of amylose-enriched genotypes.


Subject(s)
Amylose , Dioscorea , Genome-Wide Association Study , Plant Tubers , Polymorphism, Single Nucleotide , Amylose/metabolism , Dioscorea/genetics , Dioscorea/metabolism , Plant Tubers/genetics , Plant Tubers/metabolism , Plants, Genetically Modified/genetics , Genes, Plant
15.
Sci Rep ; 14(1): 13430, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38862696

ABSTRACT

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.


Subject(s)
Apigenin , Apoptosis , Glucuronates , Janus Kinase 2 , Microglia , STAT3 Transcription Factor , Signal Transduction , Animals , Apigenin/pharmacology , STAT3 Transcription Factor/metabolism , Janus Kinase 2/metabolism , Glucuronates/pharmacology , PC12 Cells , Apoptosis/drug effects , Microglia/drug effects , Microglia/metabolism , Signal Transduction/drug effects , Rats , Mice , Caspase 3/metabolism , Glucose/metabolism , Neuroprotective Agents/pharmacology , Phosphorylation/drug effects , bcl-2-Associated X Protein/metabolism , Tyrphostins/pharmacology
16.
Fundam Res ; 4(1): 103-112, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38933835

ABSTRACT

Oceanic uptake and storage of anthropogenic CO2 (CANT) are regulated by ocean circulation and ventilation. To decipher the storage and redistribution of CANT in the western North Pacific, where a major CANT sink develops, we investigated the water column carbonate system, dissolved inorganic radiocarbon and ancillary parameters in May and August 2018, spanning the Kuroshio Extension (KE, 35-39 °N), Kuroshio Recirculation (KR, 27-35 °N) and subtropical (21-27 °N) zones. Water column CANT inventories were estimated to be 40.5 ± 1.1 mol m-2 in the KR zone and 37.2 ± 0.9 mol m-2 in the subtropical zone. In comparison with historical data obtained in 2005, relatively high rates of increase of the CANT inventory of 1.05 ± 0.20 and 1.03 ± 0.12 mol m-2 yr-1 in the recent decade were obtained in the KR and subtropical zones, respectively. Our water-mass-based analyses suggest that formation and transport of subtropical mode water dominate the deep penetration, storage, and redistribution of CANT in those two regions. In the KE zone, however, both the water column CANT inventory and the decadal CANT accumulation rate were small and uncertain owing to the dynamic hydrology, where the naturally uplifting isopycnal surfaces make CANT penetration relatively shallow. The findings of this study improve the understanding of the spatiotemporal variations of CANT distribution, storage, and transport in the western North Pacific.

18.
Int J Pharm ; 661: 124397, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945463

ABSTRACT

Rhein, a natural anthraquinone compound derived from traditional Chinese medicine, exhibits potent anti-inflammatory properties via modulating the level of Reactive oxygen or nitrogen species (RONS). Nevertheless, its limited solubility in water, brief duration of plasma presence, as well as its significant systemic toxicity, pose obstacles to its in vivo usage, necessitating the creation of a reliable drug delivery platform to circumvent these difficulties. In this study, an esterase-responsive and mitochondria-targeted nano-prodrug was synthesized by conjugating Rhein with the polyethylene glycol (PEG)-modified triphenyl phosphonium (TPP) molecule, forming TPP-PEG-RH, which could spontaneously self-assemble into RPT NPs when dispersed in aqueous media. The TPP outer layer of these nanoparticles enhances their pharmacokinetic profile, facilitates efficient delivery to mitochondria, and promotes cellular uptake, thereby enabling enhanced accumulation in mitochondria and improved therapeutic effects in vitro. The decline in RONS was observed in IL-1ß-stimulated chondrocyte after RPT NPs treating. RPT NPs also exert excellent anti-inflammatory (IL-1ß, TNF-α, IL-6 and MMP-13) and antioxidative effects (Cat and Sod) via the Nrf2 signalling pathway, upregulation of cartilage related genes (Col2a1 and Acan). Moreover, RPT NPs shows protection of mitochondrial membrane potential and inhibition of chondrocyte apoptosis. Moreover, These findings suggest that the mitochondria-targeted polymer-Rhein conjugate may offer a therapeutic solution for patients suffering from chronic joint disorders, by attenuating the progression of osteoarthritis (OA).

20.
J Immunol ; 213(2): 204-213, 2024 07 15.
Article in English | MEDLINE | ID: mdl-38856712

ABSTRACT

Bats are the natural reservoir hosts of some viruses, some of which may spill over to humans and cause global-scale pandemics. Different from humans, bats may coexist with high pathogenic viruses without showing symptoms of diseases. As one of the most important first defenses, bat type I IFNs (IFN-Is) were thought to play a role during this virus coexistence and thus were studied in recent years. However, there are arguments about whether bats have a contracted genome locus or constitutively expressed IFNs, mainly due to species-specific findings. We hypothesized that because of the lack of pan-bat analysis, the common characteristics of bat IFN-Is have not been revealed yet. In this study, we characterized the IFN-I locus for nine Yangochiroptera bats and three Yinpterochiroptera bats on the basis of their high-quality bat genomes. We also compared the basal expression in six bats and compared the antiviral and antiproliferative activity and the thermostability of representative Rhinolophus bat IFNs. We found a dominance of unconventional IFNω-like responses in the IFN-I system, which is unique to bats. In contrast to IFNα-dominated IFN-I loci in the majority of other mammals, bats generally have shorter IFN-I loci with more unconventional IFNω-like genes (IFNω or related IFNαω), but with fewer or even no IFNα genes. In addition, bats generally have constitutively expressed IFNs, the highest expressed of which is more likely an IFNω-like gene. Likewise, the highly expressed IFNω-like protein also demonstrated the best antiviral activity, antiproliferative activity, or thermostability, as shown in a representative Rhinolophus bat species. Overall, we revealed pan-bat unique, to our knowledge, characteristics in the IFN-I system, which provide insights into our understanding of the innate immunity that contributes to a special coexistence between bats and viruses.


Subject(s)
Chiroptera , Interferon Type I , Chiroptera/immunology , Chiroptera/genetics , Chiroptera/virology , Animals , Interferon Type I/genetics , Interferon Type I/immunology , Humans , Antiviral Agents , Immunity, Innate/genetics , Phylogeny
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