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2.
Angew Chem Int Ed Engl ; : e202408686, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118193

RESUMO

ß-Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo- and enantioselective biocatalytic approach for preparing a broad range of ß-branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution-asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild-type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9% ee, >99:1 dr, and >99% conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74% yield, >99.9% ee, and 98:2 dr at a challenging substrate loading of 110 g L-1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution-asymmetric reductive amination reaction system.

3.
Neurosurg Rev ; 47(1): 433, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141133

RESUMO

Receptor-interacting protein kinase-3 (RIP-3) is a key component for inducing necroptosis following acute brain injury. Purpose of this study is to unveil whether serum RIP-3 levels are related to severity and clinical outcomes after human severe traumatic brain injury (sTBI). In this two-center prospective cohort study, serum RIP-3 levels were detected in 127 healthy controls coupled with 127 sTBI patients. The prognostic indicators encompassed posttraumatic 180-day mortality, overall survival and poor prognosis (defined as extended Glasgow outcome scale scores of 1-4). The prognosis associations were verified via multivariate analysis. There was a significant incremental serum RIP-3 levels in patients with sTBI, relative to the controls. RIP-3 levels of patients were independently correlated with Rotterdam Computed Tomography (CT) scores and Glasgow coma scale (GCS) scores, as well as were independently predictive of mortality, overall survival and poor prognosis. Mortality and poor prognosis were effectively predicted by serum RIP-3 levels under the receiver operating characteristic curve. Linear relationships between RIP-3 levels and their risks were verified. Mortality and poor prognosis models of serum RIP-3 levels combined with GCS and Rotterdam CT scores displayed efficient predictive abilities. The two models were graphically represented, which were of clinical stability and value by employing the calibration and decision curves. Increased serum RIP-3 levels after sTBI are closely linked to heightened trauma severity and poor prognosis, signifying that serum RIP-3 may be an encouraging biomarker for evaluating severity and predicting clinical outcome of sTBI.


Assuntos
Biomarcadores , Lesões Encefálicas Traumáticas , Proteína Serina-Treonina Quinases de Interação com Receptores , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Adulto , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/diagnóstico , Biomarcadores/sangue , Estudos Prospectivos , Proteína Serina-Treonina Quinases de Interação com Receptores/sangue , Idoso , Escala de Coma de Glasgow , Estudos de Coortes , Adulto Jovem
4.
Front Oncol ; 14: 1406512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135994

RESUMO

Background: Biliary stricture caused by malignant tumors is known as Malignant Biliary Stricture (MBS). MBS is challenging to differentiate clinically, and accurate diagnosis is crucial for patient prognosis and treatment. This study aims to identify the risk factors for malignancy in all patients diagnosed with biliary stricture by Endoscopic Retrograde Cholangiopancreatography (ERCP), and to develop an effective clinical predictive model to enhance diagnostic outcomes. Methodology: Through a retrospective study, data from 398 patients diagnosed with biliary stricture using ERCP between January 2019 and January 2023 at two institutions: the First People's Hospital affiliated with Jiangsu University and the Second People's Hospital affiliated with Soochow University. The study began with a preliminary screening of risk factors using univariate regression. Lasso regression was then applied for feature selection. The dataset was divided into a training set and a validation set in an 8:2 ratio. We analyzed the selected features using seven machine learning algorithms. The best model was selected based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC) and other evaluation indicators. We further evaluated the model's accuracy using calibration curves and confusion matrices. Additionally, we used the SHAP method for interpretability and visualization of the model's predictions. Results: RF model is the best model, achieved an AUROC of 0.988. Shap result indicate that age, stricture location, stricture length, carbohydrate antigen 199 (CA199), total bilirubin (TBil), alkaline phosphatase (ALP), (Direct Bilirubin) DBil/TBil, and CA199/C-Reactive Protein (CRP) were risk factors for MBS, and the CRP is a protective factor. Conclusion: The model's effectiveness and stability were confirmed, accurately identifying high-risk patients to guide clinical decisions and improve patient prognosis.

5.
J Environ Manage ; 368: 122195, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137638

RESUMO

The presence of emerging contaminants (ECs) in drinking water sources is an increasing concern, yet limited data exists on their occurrence and risk in the upper Huaihe River Basin, an important agricultural region in Central China. This study investigated 70 ECs, including pesticide and antibiotics in surface water from drinking water source areas in Nanwan Reservoir along the upper reaches of the Huaihe River Basin to prioritize the ECs based on ecological risk and health risk assessment. A total of 66 ECs were detected in the surface water at least once at the selected 38 sampling sites, with concentrations ranging from 0.04 to 2508 ng/L. Ecological risk assessment using the risk quotient (RQ) method revealed high risks (RQ > 1) from 7 ECs in the dry season and 15 ECs in the wet season, with triazine pesticides as the main contributors. Non-carcinogenic risks were below negligible levels, but carcinogenic risks from neonicotinoid and carbamate pesticides and macrolide antibiotics were concerning for teenagers. Ciprofloxacin exhibited a high level of resistance risk during the wet season. A multi-indicator prioritization approach integrating occurrence, risk, and chemical property data ranked 6 pesticides and 3 antibiotics as priority pollutants. The results highlight EC contamination of drinking water sources in this agriculturally-intensive region and the need for targeted monitoring and management to protect water quality.

6.
World J Surg Oncol ; 22(1): 209, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097743

RESUMO

INTRODUCTION: Survival comparisons among patients with liver metastases from pancreatic and rectal neuroendocrine tumors (NETs) were limited, and the efficacy of observation rules in patients undergoing hepatectomy for neuroendocrine liver metastases (NELMs) was unknown. This study aims to distinguish these characteristics and clarify the effects of the observation rules on NELMs. METHODS: Clinical data were separately collected from patients with pancreatic and rectal NELMs at medical centers in both Japan and China. The Japanese cohort followed the observation rules for the resection of NELMs. A comparative analysis was conducted on clinical characteristics and prognosis features such as overall survival time (OS) and disease-free survival interval (DFS-I). RESULTS: Enrollment included 47 and 34 patients from Japan and China, respectively. Of these, 69 and 12 patients had tumors originating from the pancreas and rectum, respectively. The OS time in patients undergoing primary tumor resection was significantly longer; however, the OS time between the patients undergoing and not undergoing radical resection of liver metastasis was the same. In asynchronous NELMs, patients with rectal (R)-NELMs showed a significantly higher proportion of type III NELMs. Additionally, the median DFS-I of asynchronous R-NELMs was longer than the recommended follow-up time, with 71.4% of them classified as G2. In the Japanese cohort, patients who adhered to the observation rules exhibited a longer median DFS after hepatectomy for NELMs compared with their counterparts. CONCLUSION: Although curative surgery is crucial for primary lesions, personalized approaches are required to manage NELMs. Extended overall follow-ups and shortened follow-up intervals are recommended for G2 stage rectal NETs. The observation rules for NELMs require further validation with a larger sample size.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Retais , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Masculino , Feminino , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/mortalidade , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Hepatectomia/mortalidade , Hepatectomia/métodos , Taxa de Sobrevida , Prognóstico , Idoso , Seguimentos , Japão/epidemiologia , Adulto , China/epidemiologia , Estudos Retrospectivos
7.
Asian J Psychiatr ; 100: 104165, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39127021

RESUMO

BACKGROUND: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester. METHODS: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses. RESULTS: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted ß=0.026, 95 % CI: 0.003-0.050). CONCLUSION: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester.

8.
Int J Mol Sci ; 25(15)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39125858

RESUMO

The bottle gourd [Lagenaria siceraria (Molina) Standl.] is often utilized as a rootstock for watermelon grafting. This practice effectively mitigates the challenges associated with continuous cropping obstacles in watermelon cultivation. The lower ground temperature has a direct impact on the rootstocks' root development and nutrient absorption, ultimately leading to slower growth and even the onset of yellowing. However, the mechanisms underlying the bottle gourd's regulation of root growth in response to low root zone temperature (LRT) remain elusive. Understanding the dynamic response of bottle gourd roots to LRT stress is crucial for advancing research regarding its tolerance to low temperatures. In this study, we compared the physiological traits of bottle gourd roots under control and LRT treatments; root sample transcriptomic profiles were monitored after 0 h, 48 h and 72 h of LRT treatment. LRT stress increased the malondialdehyde (MDA) content, relative electrolyte permeability and reactive oxygen species (ROS) levels, especially H2O2 and O2-. Concurrently, LRT treatment enhanced the activities of antioxidant enzymes like superoxide dismutase (SOD) and peroxidase (POD). RNA-Seq analysis revealed the presence of 2507 and 1326 differentially expressed genes (DEGs) after 48 h and 72 h of LRT treatment, respectively. Notably, 174 and 271 transcription factors (TFs) were identified as DEGs compared to the 0 h control. We utilized quantitative real-time polymerase chain reaction (qRT-PCR) to confirm the expression patterns of DEGs belonging to the WRKY, NAC, bHLH, AP2/ERF and MYB families. Collectively, our study provides a robust foundation for the functional characterization of LRT-responsive TFs in bottle gourd roots. Furthermore, these insights may contribute to the enhancement in cold tolerance in bottle gourd-type rootstocks, thereby advancing molecular breeding efforts.


Assuntos
Cucurbitaceae , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Raízes de Plantas , Fatores de Transcrição , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Cucurbitaceae/genética , Cucurbitaceae/crescimento & desenvolvimento , Cucurbitaceae/metabolismo , Cucurbitaceae/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica/métodos , Transcriptoma , Estresse Fisiológico/genética , Espécies Reativas de Oxigênio/metabolismo , Temperatura Baixa
9.
Transl Cancer Res ; 13(7): 3922-3927, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39145092

RESUMO

Background: Angioleiomyoma is a benign lesion of mesenchymal origin, which always occurs in the uterine system. Pathologically, angioleiomyoma is usually composed of well-differentiated smooth muscle cells with few mitotic features. However, primary intracranial angioleiomyoma represents an exceedingly rare tumor, since the first case reported in 1994. Case Description: Here, we reported a case of primary intracranial angioleiomyoma, which mimicking meningioma in pre-operative images. The patient was a 42-year-old male, presented with dizziness and unsteady walking for about 6 months, without symptoms of cranial nerve deficit. Head computer tomography scan showed a well-defined lesion adjacent to right brain stem with high intensity. Contrast brain magnetic resonance imaging (MRI) scan exhibited an extra-axial mass with homogeneous enhancement located at the right pontine, presented as meningioma features; however, other tumors including lymphoma should be differentiated as well. The patient underwent sub-temporal craniotomy for the tumor resection. Histological analysis confirmed the diagnosis of angioleiomyoma. Follow-up brain MRI scan (6 months after surgery) showed total resection of the lesion without residual. Conclusions: In summary, primary intracranial angioleiomyoma is rare. Thus, diagnosis and differential diagnosis are important before surgical resection, which was mimicking meningioma in our case. Pathological analysis could reveal spindle shaped cells with few mitotic features, and confirm the diagnosis of angioleiomyoma. Currently, the optimal therapy for primary intracranial angioleiomyoma is surgical resection, and adjuvant radiation therapy for the residual tumor. However, long-term prognosis of the disease should be monitor in the future.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39146176

RESUMO

Deep Gaussian process (DGP) models offer a powerful nonparametric approach for Bayesian inference, but exact inference is typically intractable, motivating the use of various approximations. However, existing approaches, such as mean-field Gaussian assumptions, limit the expressiveness and efficacy of DGP models, while stochastic approximation can be computationally expensive. To tackle these challenges, we introduce neural operator variational inference (NOVI) for DGPs. NOVI uses a neural generator to obtain a sampler and minimizes the regularized Stein discrepancy (RSD) between the generated distribution and true posterior in L2 space. We solve the minimax problem using Monte Carlo estimation and subsampling stochastic optimization techniques and demonstrate that the bias introduced by our method can be controlled by multiplying the Fisher divergence with a constant, which leads to robust error control and ensures the stability and precision of the algorithm. Our experiments on datasets ranging from hundreds to millions demonstrate the effectiveness and the faster convergence rate of the proposed method. We achieve a classification accuracy of 93.56 on the CIFAR10 dataset, outperforming state-of-the-art (SOTA) Gaussian process (GP) methods. We are optimistic that NOVI possesses the potential to enhance the performance of deep Bayesian nonparametric models and could have significant implications for various practical applications.

12.
Brain Behav ; 14(8): e3645, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39135280

RESUMO

BACKGROUND: The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. METHODS: Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1-weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. RESULTS: Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC-ML-DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. CONCLUSION: Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC-ML-DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.


Assuntos
Disfunção Cognitiva , Hipocampo , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Adulto , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Lateralidade Funcional/fisiologia , Cognição/fisiologia , Idoso , Testes de Estado Mental e Demência
13.
Chembiochem ; : e202400345, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39087277

RESUMO

Converting fatty acids into specialty chemicals is sustainable but hindered by the low efficiency and thermal instability of current oleic acid hydratases, along with mass transfer limitations in emulsion reactions. This study introduces an optimized continuous flow micro-reactor (CFMR) that efficiently transforms oleic acid at low (15 g·L-1) and high (50 g·L-1) concentrations, improving reaction efficiency and overcoming key conversion barriers. The first CFMR model showed reaction speeds surpassing traditional batch stirred tank reactors (BSTR). Optimizations were performed on three key components: liquid storage, mixer, and reaction section of the CFMR, with each round's best conditions carried into the next. This achieved a space-time yield of 597 g·L-1·d-1 at a 15 g·L-1 oleic acid load. To further enhance the yield, we optimized the emulsifier system to solve incomplete emulsification and developed a two-component feed microreactor (TCFMR) that addressed substrate and product inhibition at high loads, reaching a 91% conversion of 50 g·L-1 oleic acid in 30 minutes, with a space-time yield of 2312 g·L-1·d-1. These advancements represent significant progress in utilizing fatty acids and advancing sustainable chemical synthesis.

14.
J Pain Res ; 17: 2495-2505, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100139

RESUMO

Background: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.

15.
Am J Transl Res ; 16(7): 2953-2962, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39114726

RESUMO

Objectives To assess the benefits of Zhuang medicine in treating rheumatoid arthritis (RA), with a focus on cardiac tricuspid annulus displacement and heart rate variability (HRV), thereby providing evidence supporting Zhuang medicine theories. METHODS: This retrospective study analyzed echocardiographic data and HRV of 30 healthy subjects and 60 RA patients. RA patients were divided into two groups for a 6-month treatment: 30 received iguratimod (control group), and 30 underwent combined Zhuang medicine and needle-pricking therapy (test group). Echocardiographic assessments and HRV measures were recorded both before and after treatment. RESULTS: Compared to the healthy group, RA patients showed increased late diastolic tricuspid annular velocity. However, early diastolic tricuspid annular velocity to late diastolic tricuspid annular velocity ratios, tricuspid annular plane systolic excursion (TAPSE), and the standard deviation of average normal RR intervals (SDANN) were significantly lower (all P<0.05). After treatment, the test group exhibited higher clinical efficacy (90% vs. 56.67% in the control group). Significant improvements were observed in TAPSE and HRV indices [SDANN, standard deviation of the RR intervals (SDNN), root mean square of successive RR interval differences (RMSSD), and the percentage of adjacent RR interval differences greater than 50 milliseconds (PNN50)] in the test group (all P<0.05). Additionally, a positive correlation was noted among these measurments. CONCLUSION: Zhuang medicine significantly enhances right ventricular function and autonomic balance in RA patients, thus affirming its therapeutic potential.

16.
Int J Biol Macromol ; 277(Pt 4): 134404, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111460

RESUMO

Atopic dermatitis (AD) is a prevalent chronic skin condition characterized by complex immune responses. Chamomile possesses potent anti-inflammatory properties and has been widely used in treating various skin diseases. This study aimed to assess the therapeutic benefits of chamomile volatile oil nanoemulsion gels (CVO-NEGs) for the treatment of AD. Chamomile volatile oil nanoemulsions (CVO-NEs) were prepared using the phase transition method, yielding spherical nanoparticles with a particle size of 19.07 nm. Subsequently, Bletilla striata polysaccharides were employed to encapsulate CVO-NEs, resulting in the formation of CVO-NEGs. In vivo studies demonstrated that the preparation of CVO-NEGs enhanced the biological activity of volatile oil in AD therapy. Histopathological results indicated that CVO-NEGs reduced skin damage, epidermal thickness, and mast cell infiltration. CVO-NEGs suppressed IgG production and reduced the levels of cytokines, including TNF-α, IL-4, and IFN-γ, in AD mice. Furthermore, flow cytometry revealed that CVO-NEGs were involved in regulating the differentiation of CD4+ T cell subsets. The immune imbalance of Th1/Th2 in AD mice can be controlled, resulting in a reduction in the hypersensitivity reaction caused by excessive Th2 activation. In conclusion, the present study confirms that CVO-NEGs have the potential to serve as an effective alternative treatment for AD.

17.
Blood Adv ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042883

RESUMO

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by genetic heterogeneity. The cytogenetic abnormality t(4;14) strongly predicts poor outcome in MM patients even in the era of novel drugs. Ferroptosis is a new approach to antitumor therapy, but the relationship between ferroptosis and MM cytogenetic abnormalities remains largely unclear. Here, we show that t(4;14)-positive but not t(4;14)-negative MM cells are susceptible to class II ferroptosis inducers (FINs) in a preclinical setting, which is dependent on the significant upregulation of the MM SET domain-containing protein (MMSET). Mechanistically, MMSET upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) transcription by binding to its promoter region, leading to increased polyunsaturated fatty acid (PUFA) levels and enhanced sensitivity of t(4;14)-positive MM to ferroptosis. Supplementation of PUFAs efficiently restores ferroptosis susceptibility of t(4;14)-negative MM. In addition, combination treatment of class II FINs and bortezomib in t(4;14)-positive MM attenuates cellular glutathione and induces both apoptosis and ferroptosis levels by inhibiting the increase of solute carrier family 7 member 11, demonstrating synergistic anti-tumor activity in vitro and in a xenograft model. Taken together, our findings suggest that targeting ferroptosis with class II FINs is a novel and promising therapeutic approach to improve the outcome of t(4;14)-positive MM.

18.
Phytochem Anal ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049188

RESUMO

INTRODUCTION: Rosa rugosa var. plena Rehd (CBR) and Rosa chinensis cv. "JinBian" (JBR) are two common species used in rose tea among different original species. CBR, the officially documented original plant of the rose species for food and medicinal purposes, is more costly than JBR. With increasing demand for different rose teas, it is meaningful to compare the chemical constituents for their quality control and reveal their skin-whitening components that will provide in-depth insights for the expansion of the rose tea industry. OBJECTIVE: This study aims to reveal the chemical variances between CBR and JBR and determine their skin-whitening components. METHODOLOGY: A strategy obtained by combining MS-based plant-metabolomics with spectrum-effect relationship analysis has been proposed for unveiling chemical differences between CBR and JBR and further exploring their potential skin-whitening components. RESULTS: A total of 2030 metabolites were found that revealed considerable differences between CBR and JBR. The results of bioactivity assay demonstrated that JBR exhibited stronger tyrosinase inhibition activity than CBR. Six potential skin-whitening compounds (di-O-galloyl-HHDP-glucoside, tri-O-galloyl-HHDP-glucoside, spiraeoside, quinic acid, rugosin A, and 1,2,3,6-tetra-O-galloyl-glucose) were discovered as potential tyrosinase inhibitors, via spectrum-effect relationship analysis. This is the first time that di-O-galloyl-HHDP-glucoside, tri-O-galloyl-HHDP-glucoside, rugosin A, and 1,2,3,6-tetra-O-galloyl-glucose have been reported with tyrosinase inhibitory activity. Additionally, molecular docking analysis was used to reveal the inhibition mechanism of these compounds toward tyrosinase. CONCLUSION: The finding of this study will be of great importance for the quality control of the two types of rose teas, and the revealed active ingredients will provide in-depth insights for the expansion of the rose tea industry.

19.
Front Sports Act Living ; 6: 1383228, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045568

RESUMO

Background: Lumbosacral muscle strain (LMS) is common in Chinese elite trampoline athletes. Advanced lumbar muscle activation is necessary for postural control before upper extremity voluntary movements, called anticipatory postural adjustment to reduce internal postural interference (IPI). The potential of delayed lumbar muscle activation has been reported in patients with non-specific LBP (NLBP) in response to IPI. However, it remains unknown whether this effect exists in elite trampoline athletes. There is also limited literature reporting the rehabilitation of LMS in this population. This study first aimed to explore whether elite trampoline athletes with LMS experience delayed activation of lumbar muscles under IPI. The secondary aim was to preliminarily evaluate an integrative rehabilitation program's effectiveness. Materials and methods: Ten elite trampoline athletes with LMS were recruited and received 10 sessions of integrative rehabilitation, including extracorporeal shock wave therapy, acupuncture, Tui-na, and spine function exercises. At baseline and after all sessions, the relative activation time of the lumbar muscles under IPI in a modified rapid arm-rise test was used as a primary outcome measure. The secondary measures included a visual analog scale (VAS) and a questionnaire to assess low back pain (LBP) and athletic training performance. Results: The relative activation time of the lumbar muscles under IPI was delayed at baseline, but significantly decreased after the intervention (P < 0.05). The VAS was significantly decreased after the intervention (P < 0.05). There was no significant correlation between the difference in VAS and in activation time of the lumbar muscles before and after the intervention (P > 0.05). Conclusions: Elite trampoline athletes with LMS had delayed activation in their lumbar muscles under IPI. Integrative rehabilitation was effective in LBP relief and neuromuscular control of the lumbar muscles, and impacted positively on training performance. Future studies with a larger sample size, a control group, and long-term follow-ups are needed to further examine the efficacy of integrative rehabilitation in elite trampoline athletes with LMS. Additionally, the application of this approach in athletes with LMS or LBP in other sports, particularly those involving IPI, should be explored.

20.
ACS Appl Mater Interfaces ; 16(29): 38690-38701, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38988275

RESUMO

Antireflective coatings with superhydrophobicity have many outdoor applications, such as solar photovoltaic panels and windshields. In this study, we fabricated an omnidirectional antireflective and superhydrophobic coating with good mechanical robustness and environmental durability via the spin coating technique. The coating consisted of a layer of phytic acid (PA)/polyacrylamide (PAM)/calcium ions (Ca2+) (referred to as Binder), an antireflective layer composed of chitin nanofibers (ChNFs), and a hydrophobic layer composed of methylsilanized silica (referred to as Mosil). The transmittance of a glass slide with the Binder/ChNFs/Mosil coating had a 5.2% gain at a wavelength of 550 nm, and the antireflective coating showed a water contact angle as high as 160° and a water sliding angle of 8°. The mechanical robustness and environmental durability of the coating, including resistance to peeling, dynamic impact, chemical erosion, ultraviolet (UV) irradiation, and high temperature, were evaluated. The coating retained excellent antireflective capacity and self-cleaning performance in the harsh conditions. The increase in voltage per unit area of a solar panel with a Binder/ChNFs/Mosil coating reached 0.4 mV/cm2 compared to the solar panel exposed to sunlight with an intensity of 54.3 × 103 lx. This work not only demonstrates that ChNFs can be used as raw materials to fabricate antireflective superhydrophobic coatings for outdoor applications but also provides a feasible and efficient approach to do so.

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