Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 2.159
Filter
1.
Carbohydr Polym ; 339: 122255, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823921

ABSTRACT

Mixed infectious vaginitis poses a serious threat to female reproductive health due to complex pathogenic factors, a long course and easy recurrence. Currently, antibiotic-based treatment methods are facing a crisis of drug resistance and secondary dysbiosis. Exploring effective drugs for the treatment of mixed vaginitis from Paeonia suffruticosa Andr., a natural traditional Chinese medicine with a long history of medicinal use, is a feasible treatment strategy. P. suffruticosa Andr. leaf extract (PLE) has significant anti-bacterial effects due to its rich content of polyphenols and flavonoids. The polyphenols in peony leaves have the potential to make carboxymethyl chitosan form in situ gel. In the current study, PLE and carboxymethyl chitosan were combined to develop another type of natural anti-bacterial anti-oxidant hydrogel for the treatment of mixed infectious vaginitis. Through a series of characterisations, CP had a three-dimensional network porous structure with good mechanical properties, high water absorption, long retention and a slow-release drug effect. The mixed infectious vaginitis mouse model induced by a mixture of pathogenic bacteria was used to investigate the therapeutic effects of CP in vivo. The appearance of the vagina, H&E colouring of the tissue and inflammatory factors (TNF-α, IL-6) confirm the good anti-vaginal effect of CP. Therefore, CP was expected to become an ideal effective strategy to improve mixed infection vaginitis due to its excellent hydrogel performance and remarkable ability to regulate flora.


Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Paeonia , Plant Extracts , Plant Leaves , Chitosan/chemistry , Chitosan/pharmacology , Chitosan/analogs & derivatives , Female , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Plant Leaves/chemistry , Mice , Plant Extracts/chemistry , Plant Extracts/pharmacology , Paeonia/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Vaginosis, Bacterial/drug therapy , Vaginosis, Bacterial/microbiology , Antioxidants/pharmacology , Antioxidants/chemistry
2.
Trials ; 25(1): 352, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822360

ABSTRACT

BACKGROUND: Knee osteoarthritis (KOA) is a chronic musculoskeletal disorder characterized by pain and functional impairment. Blood flow restriction (BFR) with low-load resistance training (LLRT) demonstrates a similar improvement in clinical outcomes to high-load resistance training (HLRT) in treating KOA. It has not been established whether intermittent blood flow restriction (iBFR) with LLRT can lead to clinical outcomes that are comparable to those produced by continuous blood flow restriction (cBFR) with LLRT and HLRT. The aim of the proposed study is to evaluate the efficacy of iBFR with LLRT on pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence in KOA patients. METHODS: This is a three-arm, non-inferiority, randomized controlled trial utilizing blinded assessors. Two hundred thirteen participants will be randomly allocated to one of the following three groups: iBFR group-receiving 4 months of LLRT with iBFR, twice weekly (n = 71); cBFR group-receiving 4 months of LLRT with cBFR, twice weekly (n = 71); or HLRT group-receiving 4 months of HLRT without BFR, twice weekly (n = 71). The primary outcome is pain. The secondary outcomes include the WOMAC, muscle strength, muscle mass, physical function, perceptions of discomfort and effort, and adherence. Pain and WOMAC will be measured at the baseline and 4 and 12 months after randomizations. Muscle strength, muscle mass, and physical function will be measured at the baseline and 4 months after randomizations. The perceptions of discomfort and effort will be measured during the first and final sessions. DISCUSSION: BFR with LLRT has a similar improvement in clinical outcomes as HLRT. However, cBFR may cause elevated ratings of perceived exertion and local discomfort, compromising patient tolerability and treatment adherence. If iBFR with LLRT could produce improvement in clinical outcomes analogous to those of HLRT and iBFR with LLRT, it could be considered an alternative approach for treating patients with KOA. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300072820. Registered on June 26, 2023.


Subject(s)
Blood Flow Restriction Therapy , Muscle Strength , Osteoarthritis, Knee , Resistance Training , Humans , Resistance Training/methods , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/therapy , Aged , Treatment Outcome , Blood Flow Restriction Therapy/methods , Female , Male , Middle Aged , Equivalence Trials as Topic , Pain Measurement , Regional Blood Flow , Randomized Controlled Trials as Topic , Recovery of Function , Time Factors , Knee Joint/physiopathology
3.
Article in English | MEDLINE | ID: mdl-38833395

ABSTRACT

Hashing has received significant interest in large-scale data retrieval due to its outstanding computational efficiency. Of late, numerous deep hashing approaches have emerged, which have obtained impressive performance. However, these approaches can contain ethical risks during image retrieval. To address this, we are the first to study the problem of group fairness within learning to hash and introduce a novel method termed Fairness-aware Hashing with Mixture of Experts (FATE). Specifically, FATE leverages the mixture-of-experts framework as the hashing network, where each expert contributes knowledge from an individual viewpoint, followed by aggregation using the gating mechanism. This strongly enhances the model capability, facilitating the generation of both discriminative and unbiased binary descriptors. We also incorporate fairness-aware contrastive learning, combining sensitive labels with feature similarities to ensure unbiased hash code learning. Furthermore, an adversarial learning objective condition on both deep features and hash codes is employed to further eliminate group biases. Extensive experiments on several benchmark datasets validate the superiority of the proposed FATE compared with various state-of-the-art approaches.

4.
Front Aging Neurosci ; 16: 1397896, 2024.
Article in English | MEDLINE | ID: mdl-38832074

ABSTRACT

Objectives: The altered neuromelanin in substantia nigra pars compacta (SNpc) is a valuable biomarker in the detection of early-stage Parkinson's disease (EPD). Diagnosis via visual inspection or single radiomics based method is challenging. Thus, we proposed a novel hybrid model that integrates radiomics and deep learning methodologies to automatically detect EPD based on neuromelanin-sensitive MRI, namely short-echo-time Magnitude (setMag) reconstructed from quantitative susceptibility mapping (QSM). Methods: In our study, we collected QSM images including 73 EPD patients and 65 healthy controls, which were stratified into training-validation and independent test sets with an 8:2 ratio. Twenty-four participants from another center were included as the external validation set. Our framework began with the detection of the brainstem utilizing YOLO-v5. Subsequently, a modified LeNet was applied to obtain deep learning features. Meanwhile, 1781 radiomics features were extracted, and 10 features were retained after filtering. Finally, the classified models based on radiomics features, deep learning features, and the hybrid of both were established through machine learning algorithms, respectively. The performance was mainly evaluated using accuracy, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The saliency map was used to visualize the model. Results: The hybrid feature-based support vector machine (SVM) model showed the best performance, achieving ACC of 96.3 and 95.8% in the independent test set and external validation set, respectively. The model established by hybrid features outperformed the one radiomics feature-based (NRI: 0.245, IDI: 0.112). Furthermore, the saliency map showed that the bilateral "swallow tail" sign region was significant for classification. Conclusion: The integration of deep learning and radiomic features presents a potent strategy for the computer-aided diagnosis of EPD. This study not only validates the accuracy of our proposed model but also underscores its interpretability, evidenced by differential significance across various anatomical sites.

5.
Acta Pharmacol Sin ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698214

ABSTRACT

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

6.
Heliyon ; 10(10): e31403, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803848

ABSTRACT

The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8+ T cells and activated CD4+ memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.

7.
J Hazard Mater ; 474: 134728, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38805824

ABSTRACT

Microplastics are accumulating rapidly in aquatic ecosystems, providing habitats for pathogens and vectors for antibiotic resistance genes (ARGs), potentially increasing pathogenic risks. However, few studies have considered microplastics as particulate organic matter (POM) to elucidate their pathogenic risks and underlying mechanisms. Here, we performed microcosm experiments with microplastics and natural POM (leaves, algae, soil), thoroughly investigating their distinct effects on the community compositions, functional profiles, opportunistic pathogens, and ARGs in Particle-Associated (PA) and Free-Living (FL) bacterial communities. We found that both microplastics and leaves have comparable impacts on microbial community structures and functions, enriching opportunistic pathogens and ARGs, which may pose potential environmental risks. These effects are likely driven by their influences on water properties, including dissolved organic carbon, nitrate, DO, and pH. However, microplastics uniquely promoted pathogens as keystone species and further amplified their capacity as hosts for ARGs, potentially posing a higher pathogenic risk than natural POM. Our research also emphasized the importance of considering both PA and FL bacteria when assessing microplastic impacts, as they exhibited different responses. Overall, our study elucidates the role and underlying mechanism of microplastics as an emerging POM in intensifying pathogenic risks of aquatic ecosystems in comparison with conventional natural POM.

8.
Environ Toxicol Chem ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695729

ABSTRACT

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

9.
J Multidiscip Healthc ; 17: 2371-2387, 2024.
Article in English | MEDLINE | ID: mdl-38770171

ABSTRACT

Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.

10.
Biomedicines ; 12(5)2024 May 19.
Article in English | MEDLINE | ID: mdl-38791090

ABSTRACT

AIM: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. METHODS: Chinese Han pregnant women (GDM n = 9, control n = 10) with a scheduled caesarean section delivery were recruited. A number of high-fat diet (HFD) induced-pregnancy C57BL/6 mice were chosen as an animal model of GDM. Circulating levels of CTRP6 and adiponectin were examined by ELISA. CTRP6 expression in adipose tissue and placenta were detected by real-time qPCR and WB. RESULT: Plasma CTRP6 levels were decreased during the first and second trimesters in mice, as well as the second and third trimesters in patients, while they were increased at delivery in GDM patients and mice. Plasma CTRP6 levels were significantly correlated with WBC, systolic pressure, diastolic pressure and fasting blood glucose. Moreover, CTRP6 mRNA expression in the subcutaneous (sWAT) and omental white adipose tissue (oWAT), as well as in the placenta, was significantly higher in GDM human patients at cesarean delivery. Furthermore, the mRNA expression of Ctrp6 was increased in the sWAT and visceral WAT (vWAT), whilst decreased in the interscapular brown adipose tissue (iBAT), of GDM mice at cesarean delivery. CONCLUSION: Dynamically expressed CTRP6 may be served as a candidate target for treatment of GDM.

11.
J Ethnopharmacol ; 331: 118327, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38750987

ABSTRACT

ETHNOPHARMACOLOGY RELEVANCE: Rohdea pachynema F.T.Wang & Tang (R. pachynema), is a traditional folk medicine used for the treatment of stomach pain, stomach ulcers, bruises, and skin infections in China. Some of the diseases may relate to microbial infections in traditional applications. However few reports on its antimicrobial properties and bioactive components. AIM OF THE STUDY: To identify its bioactive constituents against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo, and its mechanism. MATERIALS AND METHODS: The anti-MRSA ingredient 6α-O-[ß-D-xylopyranosyl-(1 â†’ 3)-ß-D-quinovopyranosyl]-(25S)-5α-spirostan-3ß-ol (XQS) was obtained from R. pachynema by phytochemical isolation. Subsequently, XQS underwent screening using the broth microdilution method and growth inhibition curves to assess its antibacterial activity. The mechanism of XQS was evaluated by multigeneration induction, biofilm resistance assay, scanning electron microscopy, transmission electron microscopy, and metabolomics. Additionally, a mouse skin infection model was established in vivo. RESULTS: 26 compounds were identified from the R. pachynema, in which anti-MRSA spirostane saponin (XQS) was reported for the first time with a minimum inhibitory concentration (MIC) of 8 µg/mL. XQS might bind to peptidoglycan (PGN) of the cell wall, phosphatidylglycerol (PG), and phosphatidylethanolamine (PE) of the cell membrane, then destroying the cell wall and the cell membrane, resulting in reduced membrane fluidity and membrane depolarization. Furthermore, XQS affected MRSA lipid metabolism, amino acid metabolism, and ABC transporters by metabolomics analysis, which targeted cell walls and membranes causing less susceptibility to drug resistance. Furthermore, XQS (8 mg/kg) recovered skin wounds in mice infected by MRSA effectively, superior to vancomycin (8 mg/kg). CONCLUSIONS: XQS showed anti-MRSA bioactivity in vitro and in vivo, and its mechanism association with cell walls and membranes was reported for the first, which supported the traditional uses of R. pachynema and explained its sensitivity to MRSA.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , Microbial Sensitivity Tests , Saponins , Animals , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Mice , Saponins/pharmacology , Saponins/isolation & purification , Spirostans/pharmacology , Spirostans/isolation & purification , Biofilms/drug effects , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Female , Fishes , Male
12.
Front Immunol ; 15: 1369116, 2024.
Article in English | MEDLINE | ID: mdl-38711505

ABSTRACT

Objective: Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome-metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS. Methods: To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites. Results: A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria Ruminococcus gnavus and the promotion of the probiotic bacteria Bacteroides uniformis. Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored. Conclusion: In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.


Subject(s)
Feces , Gastrointestinal Microbiome , Metabolome , Probiotics , Spondylitis, Ankylosing , Humans , Spondylitis, Ankylosing/microbiology , Spondylitis, Ankylosing/metabolism , Spondylitis, Ankylosing/immunology , Male , Female , Adult , Feces/microbiology , Metagenomics/methods , Middle Aged , Prospective Studies , Metabolomics , Bacteria/metabolism , Bacteria/classification , Bacteria/isolation & purification , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/pharmacology
13.
Front Surg ; 11: 1367059, 2024.
Article in English | MEDLINE | ID: mdl-38712336

ABSTRACT

Epithelioid hemangioendothelioma (EHE) is a rare low-grade malignant vascular tumor. It mainly occurs in the liver, lungs, bones, and other parts of the body. Reports of epithelioid hemangioendothelioma in the parotid gland are rare in both domestic and international literature. Here, we present a case report of a parotid gland epithelioid hemangioendothelioma, including its complete clinical course and imaging findings, to improve the diagnosis and treatment of this unusual disease. Case presentation: The patient, a 75-year-old female, presented with a swelling around the right ear for 2 months and pain for 20 days. Enhanced MRI of the parotid gland revealed a well-defined, round mass with homogeneous signal intensity. The mass showed low signal intensity on T1-weighted imaging, high signal intensity on T2-weighted imaging, nodular low signal intensity within, significant high signal intensity on DWI sequence, low signal intensity on ADC sequence, and heterogeneous enhancement in the arterial phase after intravenous injection of Gd-DTPA. Nodular non-enhancing low signal intensity was observed internally, and slight clearance was seen in the venous phase. The initial diagnosis before surgery was a benign lesion, but after histopathological and immunohistochemical examination, it was confirmed as epithelioid hemangioendothelioma. Intervention: Complete tumor resection was performed. Results: The patient experienced a favorable recovery, with meticulous follow-up conducted for up to 1 year revealing no signs of recurrence or metastasis. Continued patient surveillance is ongoing to substantiate and validate the long-term efficacy of the treatment. Conclusion: Due to the extreme rarity of parotid gland epithelioid hemangioendothelioma, it often leads to a high misdiagnosis rate. The most common misdiagnosis is salivary gland lymphoma, followed by epithelioid hemangiosarcoma. When the lesion is multifocal, fusiform, with internal necrosis, and shows punctate low signal intensity on T2-weighted imaging, significant enhancement in the arterial phase, particularly with more pronounced peripheral enhancement, and persistent enhancement in the venous and delayed phases, epithelioid hemangioendothelioma should be considered. However, the current clinical diagnosis of epithelioid hemangioendothelioma still primarily relies on immunohistochemical methods.

15.
Food Res Int ; 187: 114395, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38763655

ABSTRACT

Pectic polysaccharides are one of the most vital functional ingredients in quinoa microgreens, which exhibit numerous health-promoting benefits. Nevertheless, the detailed information about the structure-function relationships of pectic polysaccharides from quinoa microgreens (QMP) remains unknown, thereby largely restricting their applications as functional foods or fortified ingredients. Therefore, to unveil the possible structure-function relationships of QMP, the mild alkali de-esterification was utilized to modify QMP, and then the correlations of esterification degrees of native and modified QMPs to their biological functions were systematically investigated. The results showed that the modified QMPs with different esterification degrees were successfully prepared by the mild alkali treatment, and the primary chemical structure (e.g., compositional monosaccharides and glycosidic linkages) of the native QMP was overall stable after the de-esterified modification. Furthermore, the results revealed that the antioxidant capacity, antiglycation effect, prebiotic potential, and immunostimulatory activity of the native QMP were negatively correlated to its esterification degree. In addition, both native and modified QMPs exerted immunostimulatory effects through activating the TLR4/NF-κB signaling pathway. These results are conducive to unveiling the precise structure-function relationships of QMP, and can also promote its applications as functional foods or fortified ingredients.


Subject(s)
Antioxidants , Chenopodium quinoa , Esterification , Chenopodium quinoa/chemistry , Structure-Activity Relationship , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/analysis , Pectins/chemistry , Polysaccharides/chemistry , Prebiotics , Animals , Mice , Functional Food , RAW 264.7 Cells , NF-kappa B/metabolism
16.
Mol Neurobiol ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767837

ABSTRACT

Cerebral ischemia-reperfusion injury produces excessive reactive oxygen and nitrogen species, including superoxide, nitric oxide, and peroxynitrite (ONOO-). We recently developed a new ONOO--triggered metal-free carbon monoxide donor (PCOD585), exhibiting a notable neuroprotective outcome on the rat middle cerebral artery occlusion model and rendering an exciting intervention opportunity toward ischemia-induced brain injuries. However, its therapeutic mechanism still needs to be addressed. In the pharmacological study, we found PCOD585 inhibited neuronal Bcl2/Bax/caspase-3 apoptosis pathway in the peri-infarcted area of stroke by scavenging ONOO-. ONOO- scavenging further led to decreased Acyl-CoA synthetase long-chain family member 4 and increased glutathione peroxidase 4, to minimize lipoperoxidation. Additionally, the carbon monoxide release upon the ONOO- reaction with PCOD585 further inhibited the neuronal Iron-dependent ferroptosis associated with ischemia-reperfusion. Such a synergistic neuroprotective mechanism of PCOD585 yields as potent a neuroprotective effect as Edaravone. Additionally, PCOD585 penetrates the blood-brain barrier and reduces the degradation of zonula occludens-1 by inhibiting matrix metalloproteinase-9, thereby protecting the integrity of the blood-brain barrier. Our study provides a new perspective for developing multi-functional compounds to treat ischemic stroke.

17.
J Phys Chem Lett ; 15(20): 5467-5475, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38748088

ABSTRACT

Two-dimensional (2D) covalent organic frameworks (COFs) assembled using building blocks have been widely employed in photocatalysis due to their customizable optoelectronic characteristics and porous structure, which facilitate charge carrier and mass movement. Nevertheless, the development of COF photocatalysts encounters a continuous obstacle in enhancing the efficiency of photocatalysis, impeded by a limited comprehension of the orbital interaction between molecular fragments and linkers. In this study, we present a model that examines the interaction between molecular fragments in an imine-based COF at the frontier molecular orbital level, enabling us to comprehend the impact of manipulating linkers on light adsorption, exciton efficiency, and catalytic activity. Our findings demonstrate that altering the connecting orientation of 14 R-C=N-R imine linkers in 2D COFs can enhance solar-to-hydrogen (STH) efficiency under visible light from 2.76% to 4.24%. This research has the potential to provide a valuable model for refining photocatalysts with enhanced photocatalytic performance.

18.
ACS Biomater Sci Eng ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780535

ABSTRACT

With the utilization of advanced microfluidic techniques, the microfluidic particle counter demonstrates significant potential due to its high efficiency, precise manipulation, and portability. This work focuses on a photodetection counter based on optical absorption. To achieve precise particle detection, a Christmas tree-like structure was implemented to separate a single particle from a cluster, which was then detected in independent multiple parallel channels. The system exhibits a high degree of reliability, as evidenced by a linear correlation coefficient over 0.99 obtained during testing with gradient-concentrated beads. Furthermore, when the calculated density of NIH 3T3 cells is compared with that of a traditional flow cytometer, the system achieves a substantial agreement percentage ranging from 87.5 to 99.9%. The system's ability to perform high-throughput analysis with a high acquisition rate positions it as a promising tool for real-time point-of-care testing.

19.
Adv Mater ; : e2402695, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38742820

ABSTRACT

Flexible supercapacitors can potentially power next-generation flexible electronics. However, the mechanical and electrochemical stability of flexible supercapacitors under different flexible conditions is limited by the weak bonding between adjacent layers, posing a significant hindrance to their practical applicability. Herein, based on the uninterrupted 3D network during the growth of bacterial cellulose (BC), a flexible all-in-one supercapacitor is cultivated through a continuous biosynthesis process. This strategy ensures the continuity of the 3D network of BC throughout the material, thereby forming a continuous electrode-separator-electrode structure. Benefitting from this bioinspired structure, the all-in-one supercapacitor not only achieves a high areal capacitance (3.79 F cm-2) of electrodes but also demonstrates the integration of high tensile strength (2.15 MPa), high shear strength (more than 54.6 kPa), and high bending resistance, indicating a novel pathway toward high-performance flexible power sources.

20.
Cell Rep Med ; 5(5): 101551, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38697104

ABSTRACT

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.


Subject(s)
Artificial Intelligence , Magnetic Resonance Imaging , Humans , Prognosis , Magnetic Resonance Imaging/methods , Male , Female , Middle Aged , Adult , Lymphoma, Extranodal NK-T-Cell/diagnostic imaging , Lymphoma, Extranodal NK-T-Cell/pathology , Lymphoma, Extranodal NK-T-Cell/mortality , Lymphoma, Extranodal NK-T-Cell/diagnosis , Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...