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1.
Adv Mater ; : e2405224, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39118578

ABSTRACT

In this work, fusible microspheres loaded with radiopaque agents as an embolic agent for transcatheter arterial embolization (TAE) are developed. A poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) multi-block copolymer basing polyurethane (PCEU) is synthesized and fabricated into blank microspheres (BMs). The microspheres are elastic in compression test. A clinical contrast agent lipiodol is encapsulated in the microspheres to receive fusible radiopaque microspheres (FRMs). The sizes of FRMs are uniform and range from 142.2 to 343.1 µm. The encapsulated lipiodol acts as the plasticizer to reduce the melting temperature point (Tm) of PECU microspheres, thus, leading to the fusion of microspheres to exhibit efficient embolization in vivo. The performance of FRMs is carried out on a rabbit ear embolization model. Serious ischemic necrosis is observed and the radiopacity of FRMs sustains much longer time than that of commercial contrast agent Loversol in vivo. The fusible and radiopaque microsphere is promising to be developed as an exciting embolic agent.

2.
Braz J Med Biol Res ; 57: e13889, 2024.
Article in English | MEDLINE | ID: mdl-39194034

ABSTRACT

With the escalating incidence and mortality rates of cancer, there is an ever-growing emphasis on the research of anticancer drugs. Cordycepin, the primary nucleoside antibiotic isolated from Cordyceps militaris, has emerged as a remarkable agent for cancer prevention and treatment. Functioning as a natural targeted antitumor drug, cordycepin assumes an increasingly pivotal role in cancer therapy. This review elucidates the mechanisms of cordycepin in inhibiting tumor cell proliferation, inducing apoptosis, as well as its capabilities in suppressing angiogenesis and metastasis. Moreover, the immunomodulatory effects of cordycepin in cancer treatment are explored. Additionally, the current status, challenges, and future prospects of cordycepin application in clinical trials are briefly discussed. The objective is to provide a valuable reference for the utilization of cordycepin in cancer treatment.


Subject(s)
Apoptosis , Cell Proliferation , Deoxyadenosines , Neoplasms , Deoxyadenosines/pharmacology , Deoxyadenosines/therapeutic use , Humans , Neoplasms/drug therapy , Cell Proliferation/drug effects , Apoptosis/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neovascularization, Pathologic/drug therapy
3.
J Colloid Interface Sci ; 677(Pt B): 756-768, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39173509

ABSTRACT

The adoption of photothermal synergistic catalysis for cyclohexane oxidation can balance the advantages of high conversion of thermal catalysis and high selectivity of photocatalytic technology to achieve better catalytic performance. Here, we prepared functional carbon nitride (BCA-CN) by self-assembly strategy of ionic liquid [Bmim]CA (1-Butyl-3-methylimidazole citrate) with melamine and cyanuric acid utilizing abundant elements and anionic/cationic hydrogen bonding interactions. The introduction of [Bmim]CA embeds C-C (carbon and carbon band) and C-O-C (ether bond) structures into graphitic carbon nitride (g-C3N4) framework, significantly improving light absorption capacity and migration of photo generated charge carriers. Compared to g-C3N4, both BCA-CN increases cyclohexane conversion and KA oil (the mixture of cyclohexanol and cyclohexanone) selectivity by 1.3 times under photothermal catalysis. The surface reactions are facilitated by changing adsorption sites of cyclohexane to increase adsorption energy and obtaining more hydroxyl radicals and superoxide radicals. Furthermore, the enhanced selectivity is attributed to the difficulty in generating cyclohexanone radicals. This work offers the reference scheme for the development of efficient photothermal catalysts in the selective oxidation of cyclohexane.

4.
Article in English | MEDLINE | ID: mdl-39174346

ABSTRACT

Epigallocatechin gallate (EGCG)-based nanosystems have garnered significant attention for their ability to alleviate inflammation due to their excellent anti-inflammatory properties and enhanced drug delivery capabilities. However, the degradation of EGCG in strongly acidic environments poses a challenge for potential administration, particularly in oral formulations, where gastric resistance is essential. In this study, we develop a "disintegration and reorganization" strategy to create acid-resistant antioxidant nanoparticles (EGA NPs) based on EGCG and 5-aminosalicylic acid (5-ASA) for mitigating inflammation in colitis and acute kidney injury. At acidic pH, the ester bond in EGCG breaks down, producing two building blocks. These, together with 5-ASA and formaldehyde, form oligomers through a combination of phenol-aldehyde condensation and the Mannich reaction. The resulting oligomers self-assemble into EGA NPs, which exhibit significant stability under both acidic and neutral pH conditions. This stability makes them suitable for oral administration, allowing them to withstand harsh gastric conditions, as well as for intravenous injection. Importantly, these oligomers retain the antioxidant and anti-inflammatory properties of EGCG, effectively scavenging reactive oxygen species and reducing intracellular oxidative stress. Additionally, EGA shows potential as a drug carrier, efficiently loading the anti-inflammatory agent curcumin (Cur) to form Cur@EGA NPs. In vivo studies demonstrate the efficacy of Cur@EGA and EGA in alleviating acute colitis and kidney injury following oral and intravenous administration, respectively. These nanoparticulate formulations exhibit superior inflammation reduction compared to free Cur in vivo. Overall, our findings introduce a novel acid-resistant nanoplatform based on EGCG for the treatment of acute inflammation.

5.
Chem Commun (Camb) ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39158973

ABSTRACT

A novel synthetic route was developed for the construction of chiral cis-vicinal halohydrins derivatives through Ir/f-phamidol-catalysed asymmetric hydrogenation of corresponding α-halogenated ketones with high yields (up to 99% yield), excellent diastereoselectivities (>20 : 1 dr), enantioselectivities (up to 99% ee), and high substrate catalyst ratio (S/C = 1000).

6.
J Colloid Interface Sci ; 677(Pt B): 49-58, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39137562

ABSTRACT

To improve the electrochemical performance of positive electrode materials, constructing graded nanostructures is a worthwhile approach. This study successfully synthesized nitrogen-doped graphene quantum dots (NGQD) modified (Ni0.5Co0.5)3V2O8 on a carbon nanotube (CNT) substrate to construct self-supporting electrodes for high-performance supercapacitors. The (Ni0.5Co0.5)3V2O8 nanosheets were successfully wrapped onto the CNT surface through a solution impregnation process, which increased the specific surface area and interlayer spacing of the material. Furthermore, the electrochemical properties of the electrode material underwent significant enhancement due to the synergistic interplay between metal ions and the numerous redox centers. The embedding of the NGQD enriched the materials with active sites and further improved its specific capacity without compromising the structure intergrity of the layer configuration. Using CNT as the substrate ensured the self-supporting nature of the electrode. Consequently, the (Ni0.5Co0.5)3V2O8/NGQD@CNT composite exhibits an ultra-high specific capacitance of 3018.2 F g-1 at 1 A g-1 and 2332 F g-1 at 10 A g-1. The asymmetric supercapacitor constructed with (Ni0.5Co0.5)3V2O8/NGQD@CNT and activated carbon (AC) presented an impressive energy density of 160.2 Wh kg-1 at a power density of 800 W kg-1. After 8000 charge-discharge cycles, the capacity retention rate was 78.5 %, with a Coulo mbic efficiency consistently above 98 %.

7.
Environ Sci Technol ; 58(32): 14260-14270, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39096297

ABSTRACT

Fine-mode aerosol optical depth (fAOD) is a vital proxy for the concentration of anthropogenic aerosols in the atmosphere. Currently, the limited data length and high uncertainty of the satellite-based data diminish the applicability of fAOD for climate research. Here, we propose a novel pretrained deep learning framework that can extract information underlying each satellite pixel and use it to create new latent features that can be employed for improving retrieval accuracy in regions without in situ data. With the proposed model, we developed a new global fAOD (at 0.5 µm) data from 2001 to 2020, resulting in a 10% improvement in the overall correlation coefficient (R) during site-based independent validation and a 15% enhancement in non-AERONET site areas validation. Over the past two decades, there has been a noticeable downward trend in global fAOD (-1.39 × 10-3/year). Compared to the general deep-learning model, our method reduces the global trend's previously overestimated magnitude by 7% per year. China has experienced the most significant decline (-5.07 × 10-3/year), which is 3 times greater than the global trend. Conversely, India has shown a significant increase (7.86 × 10-4/year). This study bridges the gap between sparse in situ observations and abundant satellite measurements, thereby improving predictive models for global patterns of fAOD and other climate factors.


Subject(s)
Aerosols , Deep Learning , Atmosphere/chemistry , Environmental Monitoring/methods , Satellite Imagery
8.
Inorg Chem ; 63(33): 15467-15476, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39106315

ABSTRACT

The sluggish kinetics of the oxygen evolution reaction (OER) in alkaline water electrolysis remains a significant challenge for developing high-efficiency electrocatalytic systems. In this study, we present a three-dimensional, micrometer-sized iridium oxide (IrO2)-decorated cobalt carbonate hydroxide (IrO2-P-CoCH) electrocatalyst, which is engineered in situ on a carbon cloth (CC) substrate pretreated with atmospheric-pressure dielectric barrier discharge (DBD) plasma (PCC). The electrocatalyst features petal-like structures composed of nanosized rods, providing abundant reactive areas and sites, including the oxygen vacancy caused by the air-DBD plasma. As a result, the IrO2-P-CoCH/PCC electrocatalyst demonstrates an outstanding OER performance, with overpotentials of only 190 and 300 mV required to achieve current densities of 10 mA cm-2 (j10) and 300 mA cm-2 (j300), respectively, along with a low Tafel slope of 48.1 mV dec-1 in 1.0 M KOH. Remarkably, benefiting from rich active sites exposed on the IrO2-P-CoCH (Ir) heterostructure, the synergistic effect between IrO2 and CoCH enhances the charge delivery rates, and the IrO2-P-CoCH/PCC exhibits a superior electrocatalytic activity at a high current density (300 mV/j300) compared to the commercial benchmarked RuO2/PCC (470 mV/j300). Furthermore, the IrO2-P-CoCH/PCC electrocatalyst shows exceptional OER stability, with a mere 1.3% decrease with a current density of j10 for 100 h testing, surpassing most OER catalysts based on CC substrates. This work introduces a novel approach for designing high-performance OER electrocatalysts on flexible electrode substrates.

9.
Arch Dermatol Res ; 316(8): 563, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177825

ABSTRACT

Lower extremity nodular melanoma (NM) is a common malignant tumor with a poor prognosis. We aims to identify the prognostic factors and develop a nomogram model to predict overall survival (OS) in patients with lower extremity NM. A total of 746 patients with lower extremity NM were selected and randomly divided into a training set (522 cases) and a validation set (224 cases) from the Surveillance, Epidemiology, and End Results(SEER) database. The training set underwent univariate and multivariate Cox regression analyses to identify independent prognostic factors associated with patient outcomes, and to develop a nomogram model. The effectiveness of the nomogram was subsequently validated using the validation set. Multivariable Cox regression analysis of the training set indicated that age, ulceration, radiotherapy, chemotherapy, primary site of first malignant tumor, and Breslow thickness were independent variables associated with OS. In the training set, the area under the curve (AUC) of the nomogram for predicting 3-year and 5-year OS was 0.796 and 0.811, respectively. In the validation set, the AUC for predicting 3-year and 5-year OS was 0.694 and 0.702, respectively. The Harrell's C-index for the training set and validation set were 0.754 (95% CI: 0.721-0.787) and 0.670 (95% CI: 0.607-0.733), respectively. Calibration curves for both training and validation sets showed good agreement. In this study, we develop and validate a nomogram to predict OS in patients with lower extremity NM. The nomogram demonstrated reasonable reliability and clinical applicability. Nomograms are important tools assessing prognosis and aiding clinical decision-making.


Subject(s)
Lower Extremity , Melanoma , Nomograms , SEER Program , Skin Neoplasms , Humans , Melanoma/mortality , Melanoma/diagnosis , Melanoma/pathology , Melanoma/therapy , Melanoma/epidemiology , Male , Female , SEER Program/statistics & numerical data , Middle Aged , Prognosis , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/therapy , Aged , Adult , Aged, 80 and over
10.
Ann Med ; 56(1): 2394588, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39183465

ABSTRACT

Inflammation responses have identified as a key mediator of in various liver diseases with high morbidity and mortality. cGAS-STING signalling is essential in innate immunity since it triggers release of type I interferons and various of proinflammatory cytokines. The potential connection between cGAS-STING pathway and liver inflammatory diseases has recently been reported widely. In our review, the impact of cGAS-STING on liver inflammation and regulatory mechanism are summarized. Furthermore, many inhibitors of cGAS-STING signalling as promising agents to cure liver inflammation are also explored in detail. A comprehensive knowledge of molecular mechanisms of cGAS-STING signalling in liver inflammation is vital for exploring novel treatments and providing recommendations and perspectives for future utilization.


Subject(s)
Immunity, Innate , Liver Diseases , Membrane Proteins , Nucleotidyltransferases , Signal Transduction , Humans , Nucleotidyltransferases/metabolism , Membrane Proteins/metabolism , Membrane Proteins/immunology , Signal Transduction/immunology , Liver Diseases/metabolism , Liver Diseases/immunology , Animals , Interferon Type I/metabolism , Interferon Type I/immunology
11.
Bioinspir Biomim ; 19(5)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39094623

ABSTRACT

Nature abounds with examples of ultra-sensitive perception and agile body transformation for highly efficient predation as well as extraordinary adaptation to complex environments. Flytraps, as a representative example, could effectively detect the most minute physical stimulation of insects and respond instantly, inspiring numerous robotic designs and applications. However, current robotic flytraps face challenges in reproducing the ultra-sensitive insect-touch perception. In addition, fast and fully-covered capture of live insects with robotic flytraps remains elusive. Here we report a novel design of a robotic flytrap with an ultra-sensitive 'trichome' and bistable fast-response 'lobes'. Our results show that the 'trichome' of the proposed robotic flytrap could detect and respond to both the external stimulation of 0.45 mN and a tiny touch of a flying bee with a weight of 0.12 g. Besides, once the 'trichome' is triggered, the bistable 'lobes' could instantly close themselves in 0.2 s to form a fully-covered cage to trap the bees, and reopen to set them free after the tests. We introduce the design, modeling, optimization, and verification of the robotic flytrap, and envision broader applications of this technology in ultra-sensitive perception, fast-response grasping, and biomedical engineering studies.


Subject(s)
Flight, Animal , Robotics , Robotics/instrumentation , Robotics/methods , Animals , Flight, Animal/physiology , Touch/physiology , Equipment Design , Bees/physiology , Biomimetics/methods
12.
Glob Chang Biol ; 30(8): e17479, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39188225

ABSTRACT

Terrestrial gross primary productivity (GPP) is the largest carbon flux in the global carbon cycle and plays a crucial role in terrestrial carbon sequestration. However, historical and future global GPP estimates still vary markedly. In this study, we reduced uncertainties in global GPP estimates by employing an innovative emergent constraint method on remote sensing-based GPP datasets (RS-GPP), using ground-based estimates of GPP from flux towers as the observational constraint. Using this approach, the global GPP in 2001-2014 was estimated to be 126.8 ± 6.4 PgC year-1, compared to the original RS-GPP ensemble mean of 120.9 ± 10.6 PgC year-1, which reduced the uncertainty range by 39.6%. Independent space- and time-based (different latitudinal zones, different vegetation types, and individual year) constraints further confirmed the robustness of the global GPP estimate. Building on these insights, we extended our constraints to project global GPP estimates in 2081-2100 under various Shared Socioeconomic Pathway (SSP) scenarios: SSP126 (140.6 ± 9.3 PgC year-1), SSP245 (153.5 ± 13.4 PgC year-1), SSP370 (170.7 ± 16.9 PgC year-1), and SSP585 (194.1 ± 23.2 PgC year-1). These findings have important implications for understanding and projecting climate change, helping to develop more effective climate policies and carbon reduction strategies.


Subject(s)
Carbon Cycle , Climate Change , Remote Sensing Technology , Uncertainty , Carbon Sequestration , Models, Theoretical
13.
J Ethnopharmacol ; 336: 118728, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39186990

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. AIM OF THE STUDY: To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. MATERIALS AND METHODS: The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. RESULTS: FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and ß-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. CONCLUSIONS: FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.

14.
IEEE Rev Biomed Eng ; PP2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39186407

ABSTRACT

Brain-computer interface (BCI) is a rapidly evolving technology that has the potential to widely influence research, clinical and recreational use. Non-invasive BCI approaches are particularly common as they can impact a large number of participants safely and at a relatively low cost. Where traditional non-invasive BCIs were used for simple computer cursor tasks, it is now increasingly common for these systems to control robotic devices for complex tasks that may be useful in daily life. In this review, we provide an overview of the general BCI framework as well as the various methods that can be used to record neural activity, extract signals of interest, and decode brain states. In this context, we summarize the current state-of-the-art of non-invasive BCI research, focusing on trends in both the application of BCIs for controlling external devices and algorithm development to optimize their use. We also discuss various open-source BCI toolboxes and software, and describe their impact on the field at large.

15.
Animals (Basel) ; 14(15)2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39123753

ABSTRACT

Boar sperm quality serves as an important indicator of reproductive efficiency, playing a direct role in enhancing the output of livestock production. It has been demonstrated that mitochondrial protein translation is present in sperm and plays a crucial role in regulating sperm motility, capacitation and in vitro fertilization rate. The present study aimed to determine whether methionine supplementation enhances mitochondrial translation in boar sperm, thereby improving sperm quality. The results showed a significant elevation in the abundance of mitochondrial methionyl-tRNA formyltransferase (MTFMT), a crucial enzyme for mitochondrial protein translation, and mitochondrial DNA-encoded cytochrome c oxidase subunit 1 (COX1) in boar sperm exhibiting high motility. Both amino acids and methionine supplementation significantly enhanced boar sperm motility during storage. Moreover, methionine supplementation mitigates the loss of acrosomal integrity, enhances the expression of COX1, and boosts mitochondrial activity. Furthermore, the positive impact of methionine was negated in the presence of the mitochondrial translation inhibitor chloramphenicol. Together, these findings suggest that boar sperm may utilize methionine as a protein translation substrate to enhance sperm motility by stimulating mitochondrial protein translation. The supplementation of methionine may enhance the quality of boar sperm, thereby providing guidance for the optimization of diluent formulations for liquid storage and the identification of physiological regulators that regulate sperm motility.

16.
Int J Chron Obstruct Pulmon Dis ; 19: 1721-1739, 2024.
Article in English | MEDLINE | ID: mdl-39081776

ABSTRACT

Background: Acupuncture has been used as an adjuvant therapy for Chronic obstructive pulmonary disease (COPD). However, systematic reviews (SRs) and meta-analyses (MAs) have reported inconsistent results and unknown quality. This overview aimed to summarize the current SRs/MAs to provide evidence for the effectiveness and safety of acupuncture in the treatment of COPD. Methods: SRs/MAs were searched via eight databases from their establishment to December 31, 2023. The methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The risk of bias was assessed using the Risk of Bias in Systematic Review (ROBIS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A) to evaluate the reporting quality. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to determine the strength of evidence. In addition, we also conducted an analysis of the acupuncture points used in the primary RCTs. Results: Twenty-two SRs/MAs were included in this overview. Based on the assessment using AMSTAR 2, nineteen SRs/MAs were "critically low". Eight SRs/MAs had a low risk of bias. Based on PRISMA-A, the reporting completeness of eighteen SRs/MAs were more than 70%. As for GRADE assessment, only three outcome measures were of high quality. COPD patients can benefit from moxibustion, acupoint application, acupoint catgut embedding, manual acupuncture, and electroacupuncture, as indicated by effectiveness in measures including lung function, 6MWD, mMRC, CAT, and acute exacerbation. In addition, the efficacy of TENS needed to be further demonstrated. The commonly used acupuncture points in the RCTs include BL13, BL23, and EX-B1. Conclusion: Evidence from SRs showed that acupuncture is beneficial to lung function, acute exacerbation, 6MWD, mMRC and CAT. For SGRQ and brog scale, acupuncture should be used selectively, but this finding should still be taken with caution.


Subject(s)
Acupuncture Therapy , Lung , Pulmonary Disease, Chronic Obstructive , Systematic Reviews as Topic , Humans , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Acupuncture Therapy/adverse effects , Acupuncture Therapy/methods , Treatment Outcome , Lung/physiopathology , Meta-Analysis as Topic , Recovery of Function
18.
Biochem Biophys Res Commun ; 734: 150463, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39083969

ABSTRACT

BACKGROUND: Epithelial stromal interaction 1 (EPSTI1) plays an important role in M1 macrophages, which induce osteoclastogenesis. One recent genome-wide association study (GWAS) involving 426,824 individuals has shown that EPSTI1 is strongly associated with osteoporosis (P < 5E-8). Therefore, we speculate that EPSTI1 participates in the modulation of osteoporosis through osteoclastogenesis. The roles of EPSTI1 in osteoclastogenesis and bone resorption remain unclear. METHODS: Femur specimens were collected from osteoporotic patients and control patients. Immunofluorescence staining was used to detect the expression of EPSTI1 and signaling pathways. The osteoclastic potential of RAW264.7 cells with Sh-EPSTI1 lentivirus infection was tested using tartrate-resistant acid phosphatase (TRAP) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting was also used to examine signaling pathways. RESULTS: In this study, EPSTI1 was found to be significantly increased in tartrate-resistant acid phosphatase positive (ACP5+) osteoclasts of bone sections from osteoporotic patients. Next, we identified EPSTI1 as a positive regulator of osteoclastogenesis and osteoclast differentiation capability. Diminished EPSTI1 expression resulted in reduced osteoclastic resorption. Mechanistically, EPSTI1-driven osteoclastogenesis was regulated by NF-κB pathway, which was mediated by the phosphorylation of protein kinase R (p-PKR). Furthermore, EPSTI1 participating in the modulation of osteoporosis via PKR/NF-κB pathway was also verified in the bone samples of osteoporotic patients. CONCLUSIONS: Collectively, our findings suggest that EPSTI1 may regulate osteoclast differentiation and bone resorption through PKR/NF-κB pathway and in vivo experiments are needed to further verify EPSTI1 as the therapy target for osteoporosis.

19.
Article in English | MEDLINE | ID: mdl-38996753

ABSTRACT

Metalloproteins binding with trace elements play a crucial role in biological processes and on the contrary, those binding with exogenous heavy metals have adverse effects. However, the methods for rapid, high sensitivity and simultaneous analysis of these metalloproteins are still lacking. In this study, a fast method for simultaneously determination of both essential and toxic metal-containing proteins was developed by coupling size exclusion chromatography (SEC) with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). After optimization of the separation and detection conditions, seven metalloproteins with different molecular weight (from 16.0 to 443.0 kDa) were successfully separated within 10 min and the proteins containing iron (Fe), copper (Cu), zinc (Zn), iodine (I) and lead (Pb) elements could be simultaneously detected with the use of oxygen as the collision gas in ICP-MS/MS. Accordingly, the linear relationship between log molecular weight and retention time was established to estimate the molecular weight of unknown proteins. Thus, the trace metal and toxic metal containing proteins could be detected in a single run with high sensitivity (detection limits in the range of 0.0020-2.5 µg/mL) and good repeatability (relative standard deviations lower than 4.5 %). This method was then successfully used to analyze metal (e.g., Pb, Zn, Cu and Fe) binding proteins in the blood of Pb-intoxicated patients, and the results showed a negative correlation between the contents of zinc and lead binding proteins, which was identified to contain hemoglobin subunit. In summary, this work provided a rapid and sensitive tool for screening metal containing proteins in large number of biological samples.


Subject(s)
Chromatography, Gel , Limit of Detection , Metalloproteins , Tandem Mass Spectrometry , Chromatography, Gel/methods , Tandem Mass Spectrometry/methods , Humans , Reproducibility of Results , Metalloproteins/blood , Metalloproteins/chemistry , Metalloproteins/analysis , Linear Models , Metals, Heavy/blood , Metals, Heavy/analysis , Metals, Heavy/chemistry , Animals
20.
Adv Sci (Weinh) ; : e2402267, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39049710

ABSTRACT

Despite the proceeds in the management of acute myocardial infarction (AMI), the current therapeutic landscape still suffers from limited success in the clinic. Exaggerated inflammatory immune response and excessive oxidative stress are key pathological features aggravating myocardium damage. Herein, catalytic immunomodulatory nanocomplexes as anti-AMI therapeutics to resolve reactive oxygen species (ROS)-proinflammatory neutrophils-specific-inflammation is engineered. The nanocomplexes contain lyophilic S100A8/9 inhibitor ABR2575 in the core of nanoemulsions, which effectively disrupts the neutrophils-S100A8/A9-inflammation signaling pathway in the AMI microenvironment. Additionally, ROS scavenger ultrasmall CuxO nanoparticles are incorporated into the nanoemulsions via coordinating with SH groups of poly(ethylene glycol) (PEG)-conjugated lipids, which mimic multiple enzymes, dramatically alleviating the oxidative stress damage to myocardial tissue. This combination strategy significantly suppresses the infiltration of pro-inflammatory monocytes, macrophages, and neutrophils, as well as the secretion of inflammatory cytokines. Additionally, it potentially triggers cardiac Tert activation, which promotes myocardial function and decreases infarction size in preclinical murine AMI models. This approach offers a new nanomedicine for treating AMI, resulting in a dramatically enhanced therapeutic outcome.

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