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1.
Opt Lett ; 49(15): 4210-4213, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090896

RESUMO

The large-scale deployment of quantum secret sharing (QSS) in quantum networks is currently challenging due to the requirements for the generation and distribution of multipartite entanglement states. Here we present an efficient source-independent QSS protocol utilizing entangled photon pairs in quantum networks. Through the post-matching method, which means the measurement events in the same basis are matched, the key rate is almost independent of the number of participants. In addition, the unconditional security of our QSS against internal and external eavesdroppers can be proved by introducing an equivalent virtual protocol. Our protocol has great performance and technical advantages in future quantum networks.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39095057

RESUMO

BACKGROUND: The present study aims to evaluate the postprocessing image quality of a deep-learning (DL)-based automatic bone removal algorithm in the real clinical practice for cervical computed tomography angiography (CTA). MATERIALS AND METHODS: A total of 100 patients (31 females, 61.4 ± 12.4 years old) who had performed cervical CTA from January 2022 to July 2022 were included retrospectively. Three different types of scanners were used. Ipsilateral cervical artery was divided into 10 segments. The performance of the DL algorithm and conventional algorithm in terms of bone removal and vascular integrity was independently evaluated by two radiologists for each segment. The difference in the performance between the two algorithms was compared. Inter- and intrarater consistency were assessed, and the correlation between the degree of carotid artery stenosis and the rank of bone removal and vascular integrity was analyzed. RESULTS: Significant differences were observed in the rankings of bone removal and vascular integrity between the two algorithms on most segments on both sides. Compared to DL algorithm, the conventional algorithm showed a higher correlation between the degree of carotid artery stenosis and vascular integrity (r = -0.264 vs r = -0.180). The inter- and intrarater consistency of DL algorithm were found to be higher than or equal to those of conventional algorithm. CONCLUSIONS: The DL algorithm for bone removal in cervical CTA demonstrated significantly better performance than conventional postprocessing method, particularly in the segments with complex anatomical structures and adjacent to bone.

3.
Nat Commun ; 15(1): 6651, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39103330

RESUMO

Myocardial infarction (MI) has a 5-year mortality rate of more than 50% due to the lack of effective treatments. Interactions between cardiomyocytes and the MI microenvironment (MIM) can determine the progression and fate of infarcted myocardial tissue. Here, a specially designed Melanin-based composite nanomedicines (MCN) is developed to effectively treat MI by reprogramming the MIM. MCN is a nanocomposite composed of polydopamine (P), Prussian blue (PB) and cerium oxide (CexOy) with a Mayuan-like structure, which reprogramming the MIM by the efficient conversion of detrimental substances (H+, reactive oxygen species, and hypoxia) into beneficial status (O2 and H2O). In coronary artery ligation and ischemia reperfusion models of male mice, intravenously injecting MCN specifically targets the damaged area, resulting in restoration of cardiac function. With its promising therapeutic effects, MCN constitutes a new agent for MI treatment and demonstrates potential for clinical application.


Assuntos
Cério , Indóis , Melaninas , Infarto do Miocárdio , Nanomedicina , Polímeros , Animais , Melaninas/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Masculino , Camundongos , Nanomedicina/métodos , Indóis/química , Polímeros/química , Cério/química , Cério/farmacologia , Cério/administração & dosagem , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Nanocompostos/química , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Microambiente Celular/efeitos dos fármacos , Ferrocianetos
4.
Langmuir ; 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105694

RESUMO

The high expense associated with electrocatalysts poses a challenge to the advancement of a hydrogen-based energy economy. The utilization of nonprecious metal-based electrocatalysts that are easily prepared and cost-effective is imperative for the future sustainability of a hydrogen society. The semiconductive MoO3-x has been identified as a promising nonprecious electrocatalyst for the hydrogen evolution reaction (HER). Nevertheless, enhancing its relatively low electrocatalytic activity toward HER remains a top priority. This study illustrates the manipulation of surface ammonium ions (NH4+) to produce uniform and distinct cobalt nanoparticles (Co NPs) on active MoO3-x supports, resulting in a more effective heterostructured composite electrocatalyst for HER. The presence of NH4+ ions in the MoO3-x film was extensively examined using infrared spectroscopy, X-ray photoelectron spectroscopy, and UV-visible colorimetric techniques. Additionally, the firmly attached NH4+ ions were employed as binding sites to precipitate Co-containing complex ions. Due to the monolayer-like adsorption of NH4+ ions, only a small quantity of Co precipitate was formed, which was subsequently electrochemically transformed into Co atoms that diffused and created well-separated uniform metallic Co nanoparticles (with an average size of less than 10 nm) on the MoO3-x film. The resulting heterostructure displays a 4.5-fold increase in current density for HER compared to the MoO3-x electrocatalyst through electrochemical assessments. The enhanced catalytic activity was ascribed to the optimized adsorption/desorption of the species involved in water reduction at the heterointerfaces and improved charge transfer rates. These nanoheterostructures hold great promise for a variety of applications in heterogeneous electrocatalysis, while the novel approach could potentially direct the creation of more heterostructures.

5.
Int J Biol Macromol ; 277(Pt 3): 134315, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094886

RESUMO

With the increasing demand for food foaming, how to enhance the foaming properties of protein has gradually become the research focus. This work studied the effect of synephrine (SY) on foaming properties, structure properties, and physicochemical properties of soybean protein isolate (SPI). When the mass ratio of SY to SPI was 1:2, compared with SPI alone, the foam capacity and foam stability of the SY-SPI complex were significantly enhanced. Optical microscopy and confocal laser scanning microscope showed that the improvement in foaming performance was mainly due to the reduction of bubble size and uniform protein distribution. Circular dichroism spectrum and fluorescence spectra indicated that the hydrogen bond of SPI was destroyed and blue shifted with the addition of SY. What's more, the absolute value of Zeta potential, solubility, and hydrophobicity all increased, while the particle size decreased. As a result of molecular docking, surface hydrogen bonds, Van der Waals forces and hydrophobic interactions are the main driving forces. The addition of SY and SPI improved the specific volume and texture of angel cake. This study shows that SY has the potential to be developed into a new type of blowing agent.

6.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3887-3893, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-39099362

RESUMO

In this study, a mouse model of premature ovarian failure(POF) was constructed by injecting D-galactose(200 mg·kg~(-1)) into the back of the neck for 6 weeks. The mice were randomly divided into a normal group(group N), a model group(group M), and a Qiwei Guibao Granules group(group A, 12.87 g·kg~(-1)). Starting from the 11th day of modeling, group A was treated with Qiwei Guibao Granules by gavage for 32 days, while group M and group N were given equal volume of saline. Metabolomics analysis was used to explore the mechanism of action of Qiwei Guibao Granules in the treatment of POF. The results showed that compared with group N, the group M exhibited decreased wet weight of bilateral ovaries, increased levels of LH and FSH in serum, and significantly decreased levels of E_2 and PROG. After treatment with Qiwei Guibao Granules, compared with the group M, the group A showed a significant increase in the wet weight of bilateral ovaries, a significant decrease in the levels of FSH and LH in serum, and a significant increase in the level of E_2. Metabolomics analysis revealed 55 differential metabolites identified between group N and group M(14 upregulated and 41 downregulated compared with group N) and 82 differential metabolites identified between group M and group A(56 upregulated and 26 downregulated compared with group M), with 5 metabolites showing consistent changes between the group N vs group M. After excluding these 5 metabolites, 77 metabolites that changed after intervention with Qiwei Guibao Granules were focused on. These mainly involved histidine metabolism, glycine, serine, and threonine metabolism, and glycerophospholipid metabolism. Among them, carnosine, 1-methyl-L-histidine, imidazoleacetic acid, choline, L-threonine, beta-hydroxypyruvic acid, phosphatidylcholine, and glycerol-3-phosphate were the major differential metabolites in these three metabolic pathways. Therefore, Qiwei Guibao Granules may exert therapeutic effects on POF mice by regulating amino acid metabolism and lipid metabolism in the mouse body.


Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Insuficiência Ovariana Primária , Animais , Feminino , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Humanos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Modelos Animais de Doenças
7.
Zhongguo Gu Shang ; 37(7): 713-7, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39104074

RESUMO

OBJECTIVE: To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury. METHODS: From January 2016 to December 2020, the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed, including 35 males and 22 females, aged from 18 to 47 years old with an average of (32.9±7.9) years old. Knee function was evaluated using the International Knee Documentation Committee (IKDC) and Lysholm scores both before the operation and at the final follow-up. Meniscus healing was evaluated according to the postoperative Barrett standard. Wound healing complications, such as vascular injury, nerve injury, and lower extremity venous thrombosis, were recorded. RESULTS: All 57 patients were followed up for 12 to 58 months with an average of (38.1±14.9) months.The incisions of the patients after the operation were all Grade A healing without infection, popliteal tendon injury, blood vessel injury, nerve injury and lower extremity venous thrombosis.The IKDC score increased from (49.7±3.6) points preoperatively to (88.5±4.4) points in the final follow-up (P<0.05). The Lysholm score increased from (48.8±4.9) points preoperatively to (91.9±3.9) points at the final follow-up (P<0.05). At 3, 6 months and 1 year after operation, according to Barrett's criteria, 54 cases were clinically healed, the healing rate was 94.7% (54/57). CONCLUSION: This study preliminarily confirmed that arthroscopic suture technique can result in clinical stability through suture and fixation of the meniscus in the injured lateral popliteal tendon area. No adverse effects on knee joint function were found in the mid-term follow-up after the operation.


Assuntos
Artroscopia , Humanos , Masculino , Feminino , Adulto , Artroscopia/métodos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Estudos Retrospectivos , Lesões do Menisco Tibial/cirurgia , Tendões/cirurgia , Traumatismos dos Tendões/cirurgia
8.
Nat Commun ; 15(1): 5586, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961090

RESUMO

Lateral momentum conservation is typically kept in a non-absorptive rotationally symmetric system through mirror symmetry via Noether's theorem when illuminated by a homogeneous light wave. Therefore, it is still very challenging to break the mirror symmetry and generate a lateral optical force (LOF) in the rotationally symmetric system. Here, we report a general dynamic action in the SO(2) rotationally symmetric system, originating from the polarization-tuned mirror symmetry breaking (MSB) of the light scattering. We demonstrate theoretically and experimentally that MSB can be generally applied to the SO(2) rotationally symmetric system and tuned sinusoidally by polarization orientation, leading to a highly tunable and highly efficient LOF (9.22 pN/mW/µm-2) perpendicular to the propagation direction. The proposed MSB mechanism and LOF not only complete the sets of MSB of light-matter interaction and non-conservative force only using a plane wave but also provide extra polarization manipulation freedom.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38977296

RESUMO

BACKGROUND: Previous studies on the associations between socioeconomic status (SES) and cutaneous malignant melanoma (CMM) failed to distinguish the effects of different SES factors under an individual-data-based prospective study design. METHODS: Based on UK Biobank (UKB) and China Kadoorie Biobank (CKB), we estimated the effects of four SES factors on transitions from baseline to CMM in situ, subsequently to invasive CMM and further CMM mortality by applying multistate models. We further explored to which extent the associations between SES and CMM incidence could be explained by potential mediators including sun exposure, lifestyle and ageing in UKB. RESULTS: In multistate analyses, good household income was independently associated with an increased risk of CMM in situ (HR=1.38, 95% CI: 1.21 to 1.58) and invasive CMM (HR=1.34, 95% CI: 1.22 to 1.48) in UKB. These findings were partly validated in CKB. Especially in UKB, we observed an increased risk of CMM in situ and invasive CMM among participants with good type of house; only good education was independently associated with lower risk of evolving to invasive CMM among patients with CMM in situ (HR=0.69, 95% CI: 0.52 to 0.92); only good household income was independently associated with lower risk of CMM mortality among patients with CMM (HR=0.65, 95% CI: 0.45 to 0.95). In mediation analysis, the proportions attributable to the mediating effect were <6% for all selected variables, including self-reported sun exposure-related factors. CONCLUSION: SES factors have different effects on the incidence and progression of CMM. The association between SES and incident CMM is neither causal nor well explained by selected mediators.

10.
Neuroepidemiology ; : 1-13, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-38981460

RESUMO

INTRODUCTION: PD is a progressive neurodegeneration disease characterized by cardinal motor symptoms such as bradykinesia and tremor. The pathogenesis of PD remains unclear. It is hypothesized that immune system dysfunction may contribute to PD. Thus, autoimmune diseases may influence the risk of incident PD. METHODS: We included 398,329 participants without PD at the baseline from UK Biobank. The association between 20 autoimmune diseases with PD was examined using cox hazards regression analyses, adjusting covariates like age, sex, and smoking status in the statistical models. Sensitivity analyses were conducted, adjusting for polygenic risk score and the reported source of PD, to check the robustness. RESULTS: After an average follow-up of 13.1 ± 0.816 years, 2,245 participants were diagnosed with incident PD. After multiple comparison correction, only multiple sclerosis (MS) reached statistical significance and showed an increased risk for incident PD. Compared with non-MS patients, the risk of incident PD in MS patients was 2.57-fold with age and sex being adjusted (95% CI, 1.59-4.14; adjust p value = 0.002). After adjusting lifestyle and other factors, the hazard ratio of incident PD in MS patients was 2.49 (95% CI, 1.55-4.02; adjust p value = 0.004). Excluding the self-reported PD cases in the sensitivity analysis, MS was a detrimental factor for incident PD (HR, 2.06; 95% CI, 1.56-4.05; adjust p value = 0.004). The link between MS and PD did not reach the statistical significance in the sensitivity analysis adjusting the PRS (adjust p value = 0.95). CONCLUSION: Our study provided evidence from observational analyses that MS was associated with an increased risk of PD. Further investigations should be performed to determine the causal association and potential pathophysiology between MS and PD.

11.
Environ Pollut ; 358: 124478, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950849

RESUMO

Microplastics (MPs) and pharmaceuticals and personal care products (PPCPs) are ubiquitous in aquatic environments. Algae play an important role in aquatic environments. Thus, it is important to study the response of algae to combined exposure of MPs and PPCPs. Here, we review the effects of MPs and PPCPs on algae. First, the individual effects of MPs and PPCPs on algae were summarized. Second, the combined effects of MPs and PPCPs on algae were systematically analyzed. (1) Antagonism: ① when the MPs are too large to enter the algal cells, the adsorption of PPCPs onto MPs results in decreased the contact of MPs and PPCPs with algae; ② PPCPs and MPs have opposing actions on the same biological target; ③ MPs increase the activity of metabolic enzymes in algae, thus promoting the PPCP degradation. (2) Synergy: ① when the MPs are small enough to enter algal cells, the adsorption of PPCPs on MPs promotes the entry of PPCPs; ② when MPs are negatively charged, the adsorption of positively charged PPCPs by MPs decreases the electrostatic repulsion, increasing the interaction between algae and MPs; ③ complementary modes of action between MPs and PPCPs show combined effects on the same biological target. Third, the relative importance of the factors that impact the combined effects are evaluated using the random forest model decreased in the following order: PPCP types > algal species > MP size > MP concentration > MP types > exposure time. Finally, future directions for the combined effects of MPs and PPCPs are proposed, which will facilitate a better understanding of the environmental fate and risks of both MPs and PPCPs.

12.
Int Immunopharmacol ; 139: 112590, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38996778

RESUMO

BACKGROUND: Neonatal necrotizing enterocolitis (NEC) is one of the most prevalent and severe intestinal emergencies in newborns. The inflammatory activation of macrophages is associated with the intestinal injury of NEC. The neuroimmune regulation mediated by α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulating macrophage activation and inflammation progression, but in NEC remains unclear. This study aims to explore the effect of macrophage α7nAChR on NEC. METHODS: Mice NEC model were conducted with high-osmolarity formula feeding, hypoxia, and cold stimulation. The α7nAChR agonist PNU-282987 and mTOR inhibitor rapamycin were treated by intraperitoneal injections in mice. The expression and distribution of macrophages, α7nAChR, and phospho-mammalian target of rapamycin (p-mTOR) in the intestines of NEC patients and mice was assessed using immunohistochemistry, immunofluorescence, and flow cytometry. The expression of NLRP3, activated caspase-1 and IL-1ß in mice intestines was detected by flow cytometry, western blot or ELISA. In vitro, the mouse RAW264.7 macrophage cell line was also cultured followed by various treatments. Expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in macrophages was determined. RESULTS: Macrophages accumulated in the intestines and the expression of α7nAChR in the mucosal and submucosal layers of the intestines was increased in both the NEC patients and mice. The p-mTOR and CD68 were increased and co-localized in intestines of NEC patients. In vitro, α7nAChR agonist PNU-282987 significantly reduced the increase of NLRP3, activated caspase-1, and IL-1ß in macrophages. PNU-282987 also significantly reduced the increase of p-mTOR. The effect was blocked by AMPK inhibitor compound C. The expression of NLRP3, activated caspase-1, and IL-1ß was inhibited after mTOR inhibitor rapamycin treatment. In NEC model mice, PNU-282987 reduced the expression of p-mTOR, NLRP3, activated caspase-1, and IL-1ß in the intestine. Meanwhile, rapamycin significantly attenuated NLRP3 activation and the release of IL-1ß. Moreover, the proportion of intestinal macrophages and intestinal injury decreased after PNU-282987 treatment. CONCLUSION: Macrophage α7nAChR activation mitigates NLRP3 inflammasome activation by modulating mTOR phosphorylation, and subsequently alleviates intestinal inflammation and injury in NEC.

13.
Proc Natl Acad Sci U S A ; 121(31): e2404727121, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39052829

RESUMO

Characterizing unknown viruses is essential for understanding viral ecology and preparing against viral outbreaks. Recovering complete genome sequences from environmental samples remains computationally challenging using metagenomics, especially for low-abundance species with uneven coverage. We present an experimental method for reliably recovering complete viral genomes from complex environmental samples. Individual genomes are encapsulated into droplets and amplified using multiple displacement amplification. A unique gene detection assay, which employs an RNA-based probe and an exonuclease, selectively identifies droplets containing the target viral genome. Labeled droplets are sorted using a microfluidic sorter, and genomes are extracted for sequencing. We demonstrate this method's efficacy by spiking two known viral genomes, Simian virus 40 (SV40, 5,243 bp) and Human Adenovirus 5 (HAd5, 35,938 bp), into a sewage sample with a final abundance in the droplets of around 0.1% and 0.015%, respectively. We achieve 100% recovery of the complete sequence of the spiked-in SV40 genome with uniform coverage distribution. For the larger HAd5 genome, we cover approximately 99.4% of its sequence. Notably, genome recovery is achieved with as few as one sorted droplet, which enables the recovery of any desired genomes in complex environmental samples, regardless of their abundance. This method enables single-genome whole-genome amplification and targeting characterizations of rare viral species and will facilitate our ability to access the mutational profile in single-virus genomes and contribute to an improved understanding of viral ecology.


Assuntos
Genoma Viral , Vírus 40 dos Símios , Genoma Viral/genética , Vírus 40 dos Símios/genética , Vírus 40 dos Símios/isolamento & purificação , Metagenômica/métodos , Humanos , Adenovírus Humanos/genética , Adenovírus Humanos/isolamento & purificação , Esgotos/virologia
14.
Cell Biochem Biophys ; 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39078538

RESUMO

Systemic lupus erythematosus (SLE) is a classic autoimmune disease characterized by abnormal autoantibodies, immune complex deposition, and tissue inflammation. Despite extensive research, the exact etiology and progression of SLE remain elusive. Cytidine/uridine monophosphate kinase 2 (CMPK2), a mitochondrial nucleoside monophosphate kinase, has garnered attention for its potential involvement in the development of various diseases, including SLE, where it has been observed to be dysregulated in affected individuals. However, the specific involvement of CMPK2 in the pathogenesis of SLE remains unclear. This study aims to clarify the expression level of CMPK2 in SLE CD4+ T cells and explore its impact on CD4+ T cells. The expression levels of the CMPK2 gene and the corresponding CMPK2 protein in CD4+ T cells of SLE patients were quantified using RT-qPCR and Western blot, respectively. Immunofluorescence and RT-qPCR were used to assess the mitochondrial function of SLE CD4+ T cells. Flow cytometry was used to assess CD4+ T cell activation and apoptosis levels. The impact of CMPK2 on CD4+ T cells was investigated by gene transfection experiment. We found that CMPK2 was significantly upregulated in SLE CD4+ T cells at both gene and protein levels. These cells demonstrated aberrant mitochondrial function, as evidenced by elevated mitochondrial reactive oxygen species (mtROS) levels, mitochondrial membrane potential, and mitochondrial DNA (mtDNA) copy number. Flow cytometry revealed a notable increase in both apoptosis and activation levels of CD4+ T cells in SLE patients. Gene transfection experiments showed that suppressing CMPK2 led to a significant improvement in these conditions. These findings suggest that CMPK2 may be involved in the pathogenesis of SLE by regulating mitochondrial dysfunction in CD4+ T cells and thus affecting CD4+ T cell activation and apoptosis. Our study may provide a new target for the treatment of SLE.

15.
Int Immunopharmacol ; 140: 112825, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39079347

RESUMO

BACKGROUND: Exosomes derived from endometrial regenerative cells (ERC-Exos) can inherit the immunomodulatory function from ERCs, however, whether ERC-Exos exhibit such effect on inflammatory bowel diseases with mucosal immune dysregulation has not been explored. Insulin-like growth factor-Ⅱ (IGF2) is considered to possess the potential to induce an anti-inflammatory phenotype in immune cells. In this study, the contribution of IGF2 in mediating the protective efficacy of ERC-Exos on colitis was investigated. METHODS: Lentiviral transfection was employed to obtain IGF2-specific knockout ERC-Exos (IGF2-/--ERC-Exos). Experimental colitis mice induced by dextran sulfate sodium (DSS) were divided into the phosphate-buffered saline (untreated), ERC-Exos-treated and IGF2-/--ERC-Exos-treated groups. Colonic histopathological analysis and intestinal barrier function were explored. The infiltration of CD4+ T cells and dendritic cells (DCs) were analyzed by immunofluorescence staining and flow cytometry. The maturation and function of bone marrow-derived dendritic cells (BMDCs) in different exosome administrations were evaluated by flow cytometry, ELISA and the coculture system, respectively. RESULTS: Compared with the untreated group, ERC-Exos treatment significantly attenuated DSS-induced weight loss, bloody stools, shortened colon length, pathological damage, as well as repaired the weakened intestinal mucosal barrier, including promoting the goblet cells retention, restoring the intestinal barrier integrity and enhancing the expression of tight junction proteins, while the protective effect of exosomes was impaired with the knockout of IGF2 in ERC-Exos. Additionally, IGF2-expressing ERC-Exos decreased the proportions of Th1 and Th17, increased the proportions of Treg, as well as attenuated DC infiltration and maturation in mesenteric lymph nodes and lamina propria of the colitis mice. ERC-Exos were also observed to be phagocytosed by BMDCs and IGF2 is responsible for the modulating effect of ERC-Exos on BMDCs in vitro. CONCLUSIONS: Exosomes derived from ERCs can exert a therapeutic effect on experimental colitis with remarkable alleviation of the intestinal barrier damage and the abnormal mucosal immune responses. We emphasized that IGF2 plays a critical role for ERC-Exos mediated immunomodulatory function and protection against colitis.

16.
Nat Commun ; 15(1): 6211, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043643

RESUMO

The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.


Assuntos
Anticorpos Monoclonais , Linfócitos T CD8-Positivos , Células Matadoras Naturais , Nanopartículas , Células Matadoras Naturais/imunologia , Animais , Humanos , Camundongos , Nanopartículas/química , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Linfócitos T CD8-Positivos/imunologia , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia , Antígeno B7-H1/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Feminino , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Camundongos Endogâmicos NOD
17.
Chem Sci ; 15(29): 11311-11320, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39055035

RESUMO

Homogeneous gold catalysis has attracted much recent attention due to diverse activation modes of gold(i) towards unsaturated organic groups. Because of attractive aurophilic interaction, structural transformations of metalated species into high nuclear clusters are often proposed in gold catalysis, while to date little is known about their assembly behaviors and catalytic activity. In this work, based on stoichiometric Au(i)-mediated enyne cyclization reactions, we achieve a discrete vicinal dicarbanion-centered Au4 intermediate and three assembled Au11, Au28, and Au14 clusters held together by several aryl dicarbanions. Spectral monitoring, kinetic and theoretical investigations confirm that these discrete and assembled intermediates display four different pathways upon catalyzing the cyclization reaction of the same 1,5-enyne substrate. The discrete Au4 cluster undergoes a full protodeauration process to generate active [Au(PPh3)]+ species for catalytic use. In contrast, the net-like Au11 cluster experiences a substrate-induced dissociation to generate a semi-stable Au10 unit and an active [alkyne-Au(PPh3)]+ fragment for further transformation. The dumbbell-like Au28 cluster is prone to cleavage of the central Au-Au linkage and each Au14 moiety exposes a coordination unsaturated site to activate a substrate molecule. However, the synthetic closed-Au14 cluster with full ligand protection is no longer catalytically active.

18.
JACS Au ; 4(7): 2456-2461, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39055149

RESUMO

A domino difunctionalization of sulfonyl(acryl)imides to form ß-substituted α-aryl amides is reported. This transformation involves a 1,4-addition followed by a polar Truce-Smiles rearrangement process, entropically driven by release of SO2. A wide range of carbon- and heteroatom-based nucleophiles and sulfonyl imides were employed, allowing rapid access to highly functionalized amides. In contrast to related reactions with a radical pathway, unbiased substrates could be employed. Despite the usual requirement of an electron-poor migrating moiety for the SNAr event, we herein report unique and unprecedented vinylogous migrations of electron-neutral arenes. Additionally, a one-pot process toward ß-amido amides starting from acrylic acids has been developed.

19.
J Colloid Interface Sci ; 676: 755-762, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39059281

RESUMO

Vanadium-based metallic salts, characterized by their intrinsic low electronic conductivity, are impeding their advancement as anode materials in the realm of lithium-ion battery technology. This study presents a novel embedded anode material KVO3/NC (KVO/NC) synthesized via a sol-gel method, with KVO3 (KVO) particles in situ growing on N-doped carbon, thereby ameliorating conductivity and electrochemical performance. The findings reveal that KVO/NC composite has three lithium-ion storage sites, ultra-high cycling stability (289 mA h/g@5000 cycles@10 C@100 %), and superior rate performance (249 mA h/g@15 C; 221 mA h/g@20 C). Coupled with LiFePO4 cathode, it achieves a competitive energy density (391 W h kg-1@0.1 C; 1-3.9 V). This work reveals the practical potential of KVO/NC as a new type of lithium-ion battery anode material with high energy density and long cycle life through a series of ex situ/in situ characterizations.

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