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1.
Acupunct Med ; : 9645284241280074, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39340157

RESUMO

BACKGROUND: Sciatic nerve injury is a common form of peripheral nerve injury (PNI). It has been suggested that electroacupuncture (EA) stimulation at GB30 and ST36 can improve nerve dysfunction post-PNI. Autophagy is an important factor in the regeneration of sciatic nerves and recovery of motor function. Therefore, we investigated the biological effects of EA and examined whether these were mediated by autophagy in sciatic nerve injury. METHODS: Mechanical clamping of the sciatic nerve in Sprague-Dawley rats was performed to establish an experimental model of sciatic nerve injury. EA stimulation was administered once daily for 15 min for seven consecutive days beginning 1 week after successful modeling. The recovery of sciatic nerve function was examined via the sciatic functional index (SFI) test. Morphometric analysis was conducted by staining nerve samples with toluidine blue. Autophagy-associated protein levels were measured via Western blotting. RESULTS: EA stimulation at GB30 and ST36 significantly increased the number of myelinated fibers, axonal and fiber diameters, and the thickness of the myelin sheath in our rat model of sciatic nerve injury. In addition, EA stimulation greatly facilitated nerve regeneration following sciatic nerve injury. Moreover, sciatic nerve injury-induced autophagy was inhibited by EA stimulation. CONCLUSION: EA facilitates recovery of injured sciatic nerves and inhibits autophagy in a rat model.

2.
Curr Med Sci ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39347922

RESUMO

BACKGROUND AND OBJECTIVE: The effectiveness of radiofrequency ablation (RFA) in improving long-term survival outcomes for patients with a solitary hepatocellular carcinoma (HCC) measuring 5 cm or less remains uncertain. This study was designed to elucidate the impact of RFA therapy on the survival outcomes of these patients and to construct a prognostic model for patients following RFA. METHODS: This study was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, focusing on patients diagnosed with a solitary HCC lesion ≤5 cm in size. We compared the overall survival (OS) and cancer-specific survival (CSS) rates of these patients with those of patients who received hepatectomy, radiotherapy, or chemotherapy or who were part of a blank control group. To enhance the reliability of our findings, we employed stabilized inverse probability treatment weighting (sIPTW) and stratified analyses. Additionally, we conducted a Cox regression analysis to identify prognostic factors. XGBoost models were developed to predict 1-, 3-, and 5-year CSS. The XGBoost models were evaluated via receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) curves and so on. RESULTS: Regardless of whether the data were unadjusted or adjusted for the use of sIPTWs, the 5-year OS (46.7%) and CSS (58.9%) rates were greater in the RFA group than in the radiotherapy (27.1%/35.8%), chemotherapy (32.9%/43.7%), and blank control (18.6%/30.7%) groups, but these rates were lower than those in the hepatectomy group (69.4%/78.9%). Stratified analysis based on age and cirrhosis status revealed that RFA and hepatectomy yielded similar OS and CSS outcomes for patients with cirrhosis aged over 65 years. Age, race, marital status, grade, cirrhosis status, tumor size, and AFP level were selected to construct the XGBoost models based on the training cohort. The areas under the curve (AUCs) for 1, 3, and 5 years in the validation cohort were 0.88, 0.81, and 0.79, respectively. Calibration plots further demonstrated the consistency between the predicted and actual values in both the training and validation cohorts. CONCLUSION: RFA can improve the survival of patients diagnosed with a solitary HCC lesion ≤5 cm. In certain clinical scenarios, RFA achieves survival outcomes comparable to those of hepatectomy. The XGBoost models developed in this study performed admirably in predicting the CSS of patients with solitary HCC tumors smaller than 5 cm following RFA.

3.
J Hazard Mater ; 480: 135959, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39341196

RESUMO

Smelting sites often exhibit significant heavy metal(loid)s (HMs) contamination in the soil and groundwater, which are inevitably subjected to environmental disturbances. However, there is limited information available regarding the migration behaviors of HMs in a disturbed scenario. Thus, this work explored the migration of HMs-bearing colloids in response to freeze-thaw treatments by laboratory simulation and pore-scale study. Ultrafiltration results of soil effluents revealed that 61.5 %, 47.6 %, 68.0 %, and 59.2 % of Zn, Cd, Pb, and As were present in colloidal phase, and co-transported during treatments. Nanoparticle tracking analysis (NTA) further confirmed that freeze-thaw cycles were conducive to the generation of colloidal particles and showed the heteroagglomeration among different particles. Pore-network model (PNM) was used to quantify the soil macropore characteristics (macropore diameter, macropore number, coordination number, and Euler value) after treatments. It is evident that freeze-thaw cycles induced the formation of larger macropores while simultaneously enhancing macropore connectivity, thereby establishing an optimal pathway for colloid migration. These findings underscored the importance of environmental disturbances as a trigger for the release and migration of HMs in the smelting site, offering valuable insights for controlling HMs pollution. ENVIRONMENTAL IMPLICATION: The contaminated site has been subjected to prolonged environmental disturbances, causing the exacerbation of pollutants leaching and frequent occurrences of unstable pollution situations. This work explored the migration of HMs-bearing colloids in response to freeze-thaw treatments by laboratory simulation and pore-scale study. The distinct effects of freeze-thaw treatment on colloidal particle number concentration and macropore characteristics may explain the generation and migration of colloid-associated HMs driven by environmental disturbances. This work revealed the underlying mechanisms driving the redistribution of HMs under freeze-thaw cycles, offering valuable insights for risk assessment of soil and groundwater associated with HMs migration.

4.
Phytochemistry ; 228: 114250, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39168424

RESUMO

Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.7 macrophages.


Assuntos
Alcaloides , Interleucina-6 , Lactamas , Poríferos , Pirróis , Animais , Camundongos , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Poríferos/química , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Células RAW 264.7 , Lactamas/química , Lactamas/farmacologia , Lactamas/isolamento & purificação , Pirróis/farmacologia , Pirróis/química , Pirróis/isolamento & purificação , China , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Relação Estrutura-Atividade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Relação Dose-Resposta a Droga
5.
Opt Lett ; 49(16): 4613-4616, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146118

RESUMO

High-performance, high-volume-manufacturing Si3N4 photonics requires extremely low waveguide losses augmented with heterogeneously integrated lasers for applications beyond traditional markets of high-capacity interconnects. State-of-the-art quality factors (Q) over 200 million at 1550 nm have been shown previously; however, maintaining high Qs throughout laser fabrication has not been shown. Here, Si3N4 resonator intrinsic Qs over 100 million are demonstrated on a fully integrated heterogeneous laser platform. Qi is measured throughout laser processing steps, showing degradation down to 50 million from dry etching, metal evaporation, and ion implant steps, and controllable recovery to over 100 million from annealing at 250 ∘C-350 ∘C.

6.
Small ; 20(36): e2401674, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39077956

RESUMO

Electrochemical growth of metal nanocrystals is pivotal for material synthesis, processing, and resource recovery. Understanding the heterogeneous interface between electrolyte and electrode is crucial for nanocrystal nucleation, but the influence of this interaction is still poorly understood. This study employs advanced in situ measurements to investigate the heterogeneous nucleation of metals on solid surfaces. By observing the copper nanocrystal electrodeposition, an interphase interaction-induced nucleation mechanism highly dependent on substrate surface energy is uncovered. It shows that a high-energy (HE) electrode tended to form a polycrystalline structure, while a low-energy (LE) electrode induced a monocrystalline structure. Raman and electrochemical characterizations confirmed that HE interface enhances the interphase interaction, reducing the nucleation barrier for the sturdy nanostructures. This leads to a 30.92-52.21% reduction in the crystal layer thickness and a 19.18-31.78% increase in the charge transfer capability, promoting the formation of a uniform and compact film. The structural compactness of the early nucleated crystals enhances the deposit stability for long-duration electrodeposition. This research not only inspires comprehension of physicochemical processes correlated with heterogeneous nucleation, but also paves a new avenue for high-quality synthesis and efficient recovery of metallic nanomaterials.

7.
Sci Total Environ ; 948: 174944, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-39047821

RESUMO

The downward migration of soil heavy metal(loid)s (HMs) at smelting sites poses a significant risk to groundwater. Therefore, it is requisite for pollution control to determine the pollution characteristics of soil HMs and their migration risks to groundwater. 198 soil samples collected from a Pb-Zn smelting site were classified into 6 clusters by self-organizing map (SOM) and K-means clustering. Cd, Zn, As, and Pb were identified as the characteristic contaminants of the site. The driving factors for the heterogeneous distribution of HMs have been validated through the implementation of K-means clustering and multiple-hits calculation. Using ultrafiltration extraction and microscopic analysis, the soil colloids were identified as crucial carriers facilitating the migration of HMs. Specifically, the colloidal fractions of Cd, Zn, and As, Pb in deep soil (3-4 m) accounted for 91 %, 78 %, 88 %, and 82 %, respectively, consistently surpassing those found in topsoil (0-0.5 m). It was primarily attributed to the strong affinity of HMs toward soil colloids (franklinite, PbS, and kaolinite) and dissolved organic matter (humic acids and protein). The research findings highlight the potential risk of colloidal HMs to groundwater contamination, providing valuable insights for the development of targeted management and remediation strategies.

8.
Biomaterials ; 311: 122699, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38981153

RESUMO

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.


Assuntos
Regeneração Óssea , Homeostase , Células-Tronco Mesenquimais , Neovascularização Fisiológica , Osteogênese , Osteoporose , Impressão Tridimensional , Ratos Sprague-Dawley , Alicerces Teciduais , Animais , Regeneração Óssea/efeitos dos fármacos , Osteoporose/metabolismo , Osteoporose/terapia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Alicerces Teciduais/química , Osteogênese/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Poliésteres/química , Diferenciação Celular/efeitos dos fármacos , Feminino , Ratos , Células Progenitoras Endoteliais/metabolismo , Osso e Ossos/metabolismo
9.
Fish Shellfish Immunol ; 150: 109656, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38801844

RESUMO

Interferon regulatory factor 11 (IRF11), a fish specific member of IRF family, is a transcription factor known for its positive role in teleost antiviral defense by regulating IFN expression. Despite its recognized function, the precise mechanism of IRF11 in type I IFNs production remains largely unknown. In this study, we identified IRF11 in Japanese eel, Anguilla japonica, (AjIRF11) and determined its involvement in the later phase of fish IFN production. Our results demonstrate that IRF11-induced IFN production operates through ISRE binding. Mutations in each ISRE site within the promoter of AjIFN2 or AjIFN4 abolished IRF11-mediated activation of IFN promoters. In addition, the overexpression of AjIRF11 does not significantly impact the activation of AjIFN promoters induced by RLR-related signaling pathway proteins. Furthermore, IRF11-knockdown in ZFLs (zebrafish liver cells) has no effect on the RLRs-induced expression of zebrafish IFN-φ1 and IFN-φ3, indicating that IRF11 is not involved in the RLR-mediated IFN production. However, AjIRF11 can form transcription complexes with AjSTAT1 or AjSTAT2, or form homo- or heterodimers with AjIRF1 to stimulate the transcription of type I IFNs. Overall, it is shown in this study that IRF11 can act synergistically with STAT1 and/or STAT2 for the induction of IFN.


Assuntos
Anguilla , Proteínas de Peixes , Interferon Tipo I , Fator de Transcrição STAT1 , Fator de Transcrição STAT2 , Animais , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT2/metabolismo , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Anguilla/genética , Anguilla/imunologia , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/imunologia , Doenças dos Peixes/imunologia , Imunidade Inata/genética , Peixe-Zebra/genética , Peixe-Zebra/imunologia , Regulação da Expressão Gênica/imunologia
10.
Folia Histochem Cytobiol ; 62(1): 13-24, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38563049

RESUMO

INTRODUCTION: During sepsis, the kidney is one of the most vulnerable organs. Sepsis-associated acute kidney injury (S-AKI) is hallmarked by renal inflammation, apoptosis, and oxidative injury. Ginsenoside Rg1 (Rg1) is a natural product that possesses abundant pharmacological actions and protects against many sepsis-related diseases. Nevertheless, its role and related mechanism in S-AKI remain to be determined. MATERIALS AND METHODS: S-AKI was induced using lipopolysaccharide (LPS, 10 mg/kg) via a single intraperitoneal injection. Rg1 (200 mg/kg) was intraperitoneally administered for 3 consecutive days before LPS treatment. For histopathological examination, murine kidney tissues were stained with hematoxylin and eosin. Tubular injury score was calculated to evaluate kidney injury. Serum creatinine and BUN levels were measured for assessing renal dysfunction. The levels and activities of oxidative stress markers (MDA, 4-HNE, PC, GSH, SOD, and CAT) in renal tissue were measured by corresponding kits. Renal cell apoptosis was detected by TUNEL staining. The protein levels of apoptosis-related markers (Bcl-2, Bax, and Cleaved caspase-3), proinflammatory factors, SIRT1, IκBα, p-NF-κB p65, and NF-κB p65 in kidneys were determined using western blotting. Immunofluorescence staining was employed to assess p-NF-κB p65 expression in renal tissues. RESULTS: LPS-induced injury of kidneys and renal dysfunction in mice were ameliorated by Rg1. Rg1 also impeded LPS-evoked renal cell apoptosis in kidneys. Moreover, Rg1 attenuated LPS-triggered inflammation and oxidative stress in kidneys by inhibiting proinflammatory cytokine release, enhancing antioxidant levels and activities, and reducing lipid peroxidation. However, all these protective effects of Rg1 in LPS-induced AKI mice were reversed by EX527, an inhibitor of sirtuin 1 (SIRT1). Mechanistically, Rg1 upregulated SIRT1 protein expression, increased SIRT1 activity, and inactivated NF-κB signaling in the kidney of LPS-induced AKI mice, which was also reversed by EX527. CONCLUSIONS: Rg1 ameliorates LPS-induced kidney injury and suppresses renal inflammation, apoptosis, and oxidative stress in mice via regulating the SIRT1/NF-κB signaling.


Assuntos
Injúria Renal Aguda , Ginsenosídeos , Sepse , Animais , Camundongos , NF-kappa B/metabolismo , NF-kappa B/farmacologia , NF-kappa B/uso terapêutico , Lipopolissacarídeos/toxicidade , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Sirtuína 1/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Sepse/induzido quimicamente , Sepse/complicações , Sepse/tratamento farmacológico , Apoptose
11.
Nature ; 627(8004): 534-539, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448599

RESUMO

Numerous modern technologies are reliant on the low-phase noise and exquisite timing stability of microwave signals. Substantial progress has been made in the field of microwave photonics, whereby low-noise microwave signals are generated by the down-conversion of ultrastable optical references using a frequency comb1-3. Such systems, however, are constructed with bulk or fibre optics and are difficult to further reduce in size and power consumption. In this work we address this challenge by leveraging advances in integrated photonics to demonstrate low-noise microwave generation via two-point optical frequency division4,5. Narrow-linewidth self-injection-locked integrated lasers6,7 are stabilized to a miniature Fabry-Pérot cavity8, and the frequency gap between the lasers is divided with an efficient dark soliton frequency comb9. The stabilized output of the microcomb is photodetected to produce a microwave signal at 20 GHz with phase noise of -96 dBc Hz-1 at 100 Hz offset frequency that decreases to -135 dBc Hz-1 at 10 kHz offset-values that are unprecedented for an integrated photonic system. All photonic components can be heterogeneously integrated on a single chip, providing a significant advance for the application of photonics to high-precision navigation, communication and timing systems.

12.
CNS Neurosci Ther ; 30(3): e14652, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433011

RESUMO

AIM: This study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral hemorrhage (ICH). METHODS: Using varying doses of collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification was achieved through behavioral assays, hematoma volume, and histological evaluations. Single-cell suspensions from the hemorrhaged region of the ipsilateral striatum on day three post-ICH were profiled using single-cell RNA sequencing (scRNA-seq). Gene Ontology (GO) and gene set variation analysis (GSVA) further interpreted the differentially expressed genes (DEGs). RESULTS: Following WMH induction, there was a notable increase in the percentage of myeloid cells and oligodendrocyte precursor cells (OPCs), alongside a reduction in the percentage of neurons, microglia, and oligodendrocytes (OLGs). Post-ICH WMH showed homeostatic microglia transitioning into pro-, anti-inflammatory, and proliferative states, influencing lipid metabolic pathways. Myeloid cells amplified chemokine expression, linked with ferroptosis pathways. Macrophages exhibited M1 and M2 phenotypes, and post-WMH, macrophages displayed a predominance of M2 phenotypes, characterized by their anti-inflammatory properties. A surge in OPC proliferation aligned with enhanced ribosomal signaling, suggesting potential reparative responses post-WMH. CONCLUSION: The study offers valuable insights into WMH's complex pathophysiology following ICH, highlighting the significance and utility of scRNA-seq in understanding the cellular dynamics and contributing to future cerebrovascular research.


Assuntos
Acidente Vascular Cerebral , Substância Branca , Animais , Ratos , Acidente Vascular Cerebral/complicações , Hemorragia Cerebral/genética , Anti-Inflamatórios , Análise de Sequência de RNA
13.
Org Biomol Chem ; 22(15): 3009-3018, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38529785

RESUMO

Catalytic activity is undoubtedly a key focus in enzyme engineering. The complicated reaction conditions hinder some enzymes from industrialization even though they have relatively promising activity. This has occurred to some dehydrogenases. Hydroxysteroid dehydrogenases (HSDHs) specifically catalyze the conversion between hydroxyl and keto groups, and hold immense potential in the synthesis of steroid medicines. We underscored the importance of 7α-HSDH activity, and analyzed the overall robustness and underlying mechanisms. Employing a high-throughput screening approach, we comprehensively assessed a mutation library, and obtained a mutant with enhanced enzymatic activity and overall stability/tolerance. The superior mutant (I201M) was identified to harbor improved thermal stability, substrate susceptibility, cofactor affinity, as well as the yield. This mutant displayed a 1.88-fold increase in enzymatic activity, a 1.37-fold improvement in substrate tolerance, and a 1.45-fold increase in thermal stability when compared with the wild type (WT) enzyme. The I201M mutant showed a 2.25-fold increase in the kcat/KM ratio (indicative of a stronger binding affinity for the cofactor). This mutant did not exhibit the highest enzyme activity compared with all the tested mutants, but these improved characteristics contributed synergistically to the highest yield. When a substrate at 100 mM was present, the 24 h yield by I201M reached 89.7%, significantly higher than the 61.2% yield elicited by the WT enzyme. This is the first report revealing enhancement of the catalytic efficiency, cofactor affinity, substrate tolerance, and thermal stability of NAD(H)-dependent 7α-HSDH through a single-point mutation. The mutated enzyme reached the highest enzymatic activity of 7α-HSDH ever reported. High enzymatic activity is undoubtedly crucial for enabling the industrialization of an enzyme. Our findings demonstrated that, when compared with other mutants boasting even higher enzymatic activity, mutants with excellent overall robustness were superior for industrial applications. This principle was exemplified by highly active enzymes such as 7α-HSDH.


Assuntos
Hidroxiesteroide Desidrogenases , Mutação Puntual , Hidroxiesteroide Desidrogenases/genética , Hidroxiesteroide Desidrogenases/metabolismo , Mutação , Catálise , Cinética
14.
Opt Lett ; 49(5): 1197-1200, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426972

RESUMO

Thin-film lithium niobate (TFLN) is an attractive platform for photonic applications on account of its wide bandgap, its large electro-optic coefficient, and its large nonlinearity. Since these characteristics are used in systems that require a coherent light source, size, weight, power, and cost can be reduced and reliability enhanced by combining TFLN processing and heterogeneous laser fabrication. Here, we report the fabrication of laser devices on a TFLN wafer and also the coprocessing of five different GaAs-based III-V epitaxial structures, including InGaAs quantum wells and InAs quantum dots. Lasing is observed at wavelengths near 930, 1030, and 1180 nm, which, if frequency-doubled using TFLN, would produce blue, green, and orange visible light. A single-sided power over 25 mW is measured with an integrating sphere.

15.
Biomaterials ; 306: 122483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330742

RESUMO

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".


Assuntos
Osteoartrite , Fatores de Transcrição , Animais , Humanos , Camundongos , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Proteínas Nucleares/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/metabolismo , Fatores de Transcrição/metabolismo
16.
J Nat Prod ; 87(2): 396-403, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38330072

RESUMO

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.


Assuntos
Dysidea , Poríferos , Sesquiterpenos , Animais , Dysidea/química , Poríferos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Anti-Inflamatórios/farmacologia , NF-kappa B , Estrutura Molecular
17.
Phytochemistry ; 220: 114017, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342290

RESUMO

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.


Assuntos
Alcaloides , Antineoplásicos , Poríferos , Animais , Espectroscopia de Ressonância Magnética , Antineoplásicos/química , Alcaloides/química , China , Estrutura Molecular
18.
Adv Mater ; 36(6): e2305162, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37708316

RESUMO

Fenton reactions are inefficient because the Fe(II) catalyst cannot be recycled in time due to the lack of a rapid electron transport pathway. This results in huge H2 O2 wastage in industrial applications. Here, it is shown that a sustainable heterogeneous Fenton system is attainable by enhancing the ligand-to-metal charge-transfer (LMCT) excited-state lifetime in Fe-gallate complex. By engineering oxygen defects in the complex, the lifetime is improved from 10-90 ps. The lengthened lifetime ensures sufficient concentrations of excited-states for an efficient Fe cycle, realizing previously unattainable H2 O2 activation kinetics and hydroxyl radical (• OH) productivity. Spectroscopic and electrochemical studies show the cyclic reaction mechanism involves in situ Fe(II) regeneration and synchronous supply of oxygen atoms from water to recover dissociated Fe─O bonds. Trace amounts of this catalyst effectively destroy two drug-resistant bacteria even after eight reaction cycles. This work reveals the link among LMCT excited-state lifetime, Fe cycle, and catalytic activity and stability, with implications for de novo design of efficient and sustainable Fenton-like processes.

19.
J Environ Sci (China) ; 139: 1-11, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105037

RESUMO

The lack of understanding of heavy metal speciation and solubility control mechanisms in smelting soils limits the effective pollution control. In this study smelting soils were investigated by an advanced mineralogical analysis (AMICS), leaching tests and thermodynamic modelling. The aims were to identify the partitioning and release behaviour of Pb, Zn, Cd and As. The integration of multiple techniques was necessary and displayed coherent results. In addition to the residual fraction, Pb and Zn were predominantly associated with reducible fractions, and As primarily existed as the crystalline iron oxide-bound fractions. AMICS quantitative analysis further confirmed that Fe oxyhydroxides were the common dominant phase for As, Cd, Pb and Zn. In addition, a metal arsenate (paulmooreite) was an important mineral host for Pb and As. The pH-stat leaching indicted that the release of Pb, Zn and Cd increased towards low pH values while release of As increased towards high pH values. The separate leaching schemes were associated with the geochemical behaviour under the control of minerals and were confirmed by thermodynamic modelling. PHREEQC calculations suggested that the formation of arsenate minerals (schultenite, mimetite and koritnigite) and the binding to Fe oxyhydroxides synchronously controlled the release of Pb, Zn, Cd and As. Our results emphasized the governing role of Fe oxyhydroxides and secondary insoluble minerals in natural attenuation of heavy metals, which provides a novelty strategy for the stabilization of multi-metals in smelting sites.


Assuntos
Metais Pesados , Poluentes do Solo , Zinco/análise , Arseniatos , Chumbo/análise , Cádmio/análise , Solo/química , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Minerais , China
20.
Sci Rep ; 13(1): 19203, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932351

RESUMO

Zinc toxicity affects crop productivity and threatens food security and human health worldwide. Unfortunately, the accumulation patterns of zinc and the harmful effects of excessive zinc on sweet potato have not been well explored. In the present research, two genotypes of sweet potato varieties with different accumulation patterns of zinc were selected to analyze the effects of excessive zinc on sweet potato via hydroponic and field cultivation experiments. The results indicated that the transfer coefficient was closely related to the zinc concentration in the storage roots of sweet potato. Excessive zinc inhibited the growth of sweet potato plants by causing imbalanced mineral concentrations, destroying the cellular structure and reducing photosynthesis. Furthermore, a total of 17,945 differentially expressed genes were identified in the two genotypes under zinc stress by transcriptomic analysis. Differentially expressed genes involved in the absorption and transport of zinc, defense networks and transcription factors played important roles in the response to zinc stress. In conclusion, this study provides a reference for the selection of sweet potato varieties in zinc contaminated soil and lays a foundation for investigating the tolerance of sweet potato to excessive zinc, which is meaningful for environmental safety and human health.


Assuntos
Ipomoea batatas , Humanos , Ipomoea batatas/genética , Transcriptoma , Zinco , Perfilação da Expressão Gênica , Fotossíntese
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