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1.
J Environ Sci (China) ; 147: 512-522, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39003067

RESUMO

To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.


Assuntos
Monitoramento Ambiental , Aprendizado de Máquina , Plásticos , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Monitoramento Ambiental/métodos , Plásticos/análise , Análise dos Mínimos Quadrados , Análise Discriminante , Cor
2.
J Environ Sci (China) ; 149: 374-385, 2025 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39181650

RESUMO

Electrocatalytic reduction of nitrate to ammonia has been considered a promising and sustainable pathway for pollutant treatment and ammonia has significant potential as a clean energy. Therefore, the method has received much attention. In this work, Cu/Fe 2D bimetallic metal-organic frameworks were synthesized by a facile method applied as cathode materials without high-temperature carbonization. Bimetallic centers (Cu, Fe) with enhanced intrinsic activity demonstrated higher removal efficiency. Meanwhile, the 2D nanosheet reduced the mass transfer barrier between the catalyst and nitrate and increased the reaction kinetics. Therefore, the catalysts with a 2D structure showed much better removal efficiency than other structures (3D MOFs and Bulk MOFs). Under optimal conditions, Cu/Fe-2D MOF exhibited high nitrate removal efficiency (87.8%) and ammonium selectivity (89.3%) simultaneously. The ammonium yielded up to significantly 907.2 µg/(hr·mgcat) (7793.8 µg/(hr·mgmetal)) with Faradaic efficiency of 62.8% at an initial 100 mg N/L. The catalyst was proved to have good stability and was recycled 15 times with excellent effect. DFT simulations confirm the reduced Gibbs free energy of Cu/Fe-2D MOF. This study demonstrates the promising application of Cu/Fe-2D MOF in nitrate reduction to ammonia and provides new insights for the design of efficient electrode materials.


Assuntos
Amônia , Cobre , Ferro , Estruturas Metalorgânicas , Nitratos , Poluentes Químicos da Água , Amônia/química , Cobre/química , Nitratos/química , Estruturas Metalorgânicas/química , Ferro/química , Poluentes Químicos da Água/química , Catálise , Modelos Químicos , Oxirredução , Cinética
3.
J Food Sci Technol ; 61(12): 2377-2387, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39431184

RESUMO

Camelina sativa oil (CSO) and Semen Ziziphi Spinosae oil (SZSO) are functional oils that have beneficial effects on brain health. This study evaluated the sedative and hypnotic effects of vegetable oils with various n - 6/n - 3 polyunsaturated fatty acids (PUFA) ratios and ɑ-linolenic acid (ALA) contents to mice. The n - 6/n - 3 PUFA ratios of CSO (CSO:SZSO = 1:0, 1.8 g/kg), SZSO (CSO:SZSO = 0:1, 1.8 g/kg), CSO-SZSO-L (CSO:SZSO = 1:1, 1.8 g/kg), and CSO-SZSO-H (CSO:SZSO = 1:1, 3.6 g/kg) were 0.51, 140, 1.69, and 1.69, respectively. The doses of ALA administered to mice with p-chlorophenylalanine-induced insomnia were approximately 0.64, 50 × 10-4, 0.32, and 0.64 g/kg, respectively. The mice were administered CSO, SZSO, and a low-dose combination of CSO and SZSO for seven days with no obvious hypnotic effects. However, the administration of a high-dose combination of CSO and SZSO significantly prolonged sleep duration in mice with induced insomnia and inhibited the serum levels of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol. Interestingly, there were no significant effects on the structure and function of the hippocampal tissue. The results indicated that the anti-insomnia effects of these vegetable oils were positively correlated with a low n - 6/n - 3 PUFA ratio and the absolute amount of ALA. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-06004-1.

4.
Int Immunopharmacol ; 143(Pt 1): 113320, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39378653

RESUMO

We previously discovered that macrophages (MΦs), especially tumor-associated MΦs (tMΦs), contribute to chemotherapy resistance in multiple myeloma (MM). However, the mechanism underlying MΦ-mediated chemotherapy resistance in MM needs further elucidation, and the identification of factors that preferentially abrogate MΦ-induced inhibition of MM chemotherapy may have important clinical significance. In this study, we showed that the expression of FASN and SCD2, the enzymes that synthesize palmitic acid and convert it to palmitoleic acid, was decreased in tMΦs compared with MΦs. Interestingly, palmitic acid abrogated the MΦ-mediated protection of MM cells from the effects of bortezomib and melphalan in vitro. Combination treatment with palmitic acid and bortezomib or melphalan further inhibited MM tumor growth in vivo. Mechanistically, palmitic acid treatment increased ALOX12 expression in MΦs. ALOX12 inhibition partially abrogated the palmitic acid-induced decrease in MΦ-mediated MM cell survival. Palmitic acid treatment inhibited AMPK signaling in MΦs, and ALOX12 knockdown activated the AMPK signaling pathway in MΦs. AMPK inhibition decreased the MΦ-mediated protection of drug-treated MM cells, and AMPK activation partially abolished the palmitic acid-induced inhibition of MΦ-mediated protection. ALOX12 converts arachidonic acid (AA) to 12-HETE. Moreover, treatment with AA but not 12-HETE partially abrogated the inhibitory effect of palmitic acid on MΦ-mediated MM cell survival in response to bortezomib or melphalan. Overall, we identified palmitic acid as a factor that inhibits MΦ-mediated resistance to bortezomib and melphalan in MM, which may have clinical significance.

5.
Chem Rev ; 124(19): 10619-10622, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39380397
6.
Neurol Sci ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382625

RESUMO

BACKGROUND: Large Hemispheric Infarction (LHI) is a devastating disease with high mortality. This study aimed to use electroencephalography (EEG) to evaluate the death risk of LHI patients and identify suitable evaluation time. METHODS: This study retrospectively collected clinical and EEG data from 73 LHI patients, dividing them into death and survival group at discharge. EEG data was classified as 1-5 days and 6-14 days after onset according to the time intervals of cerebral edema. Regression and receiver operator characteristic curve (ROC) analysis were applied to explore the impact of temporal changes in various EEG and clinical features on death. RESULTS: The areas under ROC curve (AUC) of death prediction for non-α frequency on non-infarct side at 6-14 days after onset was significantly higher than that at 1-5 days (p = 0.004). And there was no significant difference between the AUC of seizure activity for death prediction at 1-5 days and 6-14 days (p = 0.418). Multivariate regression analysis revealed that non-α frequency on non-infarct side and seizure activity at 6-14 days after onset were the independent risk factors for the death of LHI patients. Additionally, above two EEG features significantly improved the death predictive efficacy of clinical features in LHI patients with the integrated discrimination improvement index (IDI) of 0.174 (p = 0.015) and the net reclassification improvement (NRI) of 1.314 (p<0.001). CONCLUSIONS: Non-α frequency on non-infarct side and seizure activity were reliable indicators for death prediction. 6-14 days after onset was the better time window for death evaluation of LHI patients through EEG.

7.
Signal Transduct Target Ther ; 9(1): 281, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39384753

RESUMO

Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.


Assuntos
Proteína Axina , Fator Regulador 3 de Interferon , Proteína Axina/genética , Proteína Axina/imunologia , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/imunologia , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/patologia , Imunidade Inata/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/imunologia , Animais , Ubiquitinação/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Células HEK293 , Camundongos , Antivirais/farmacologia , Separação de Fases , Fragmentos de Peptídeos , Sialoglicoproteínas
8.
Am J Transl Res ; 16(9): 4479-4491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39398595

RESUMO

OBJECTIVES: To analyze the factors influencing chronic pain in patients with knee osteoarthritis after total knee replacement surgery (TKRS) and to construct a nomogram risk prediction model, providing an economically effective screening method for clinical use. METHODS: This retrospective study included 100 consecutive patients at the Jinan Central Hospital, with knee osteoarthritis who underwent TKRS from January 2023 to December 2023. Patients were divided into the observation group (n=55) and the control group (n=45) based on the presence of chronic pain. Logistic regression was performed to explore factors associated with chronic pain, including medical records, laboratory data, previous history, and independent clinical risk factors. The identified independent factors were then incorporated to construct a nomogram for chronic pain prediction. RESULTS: Six variables were identified as independent predictors of chronic pain after TKRS: age, BMI, diabetes, severity of preoperative pain, severity of postoperative acute pain, and postoperative wound infection (P<0.05). The area under the curve (AUC) of this nomogram was 0.836 [95% confidence interval (CI): 0.615-0.884], demonstrating good calibration and clinical practicability. CONCLUSION: Age, BMI, diabetes, severity of preoperative pain, severity of postoperative acute pain, and postoperative wound infection are risk factors for chronic pain after TKRS. The predictive nomogram developed in this study shows good prediction ability and accuracy for chronic pain in patients with knee osteoarthritis after surgery.

9.
RSC Adv ; 14(44): 32221-32228, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39399255

RESUMO

This study reports the synthesis and photophysical analysis of three isomeric compounds, namely 3Fmo, 3Fmm, and 3Fmp, which were engineered using carbazole as the electron donor, phthalimide as the electron acceptor, and a benzene ring as the bridging moiety. Among these, 3Fmm was distinguished by its ability to exhibit immediate room-temperature white phosphorescence following the cessation of UV illumination, whereas 3Fmo and 3Fmp demonstrated TADF properties. Crystallographic analysis revealed unique intermolecular π-π stacking interactions within 3Fmm, absent in the other two isomers. Advanced TD-DFT computations indicated that such π-π stacking in 3Fmm not only facilitates intersystem crossing but also effectively reduces the free volume within the crystal, leading to a decrease in non-radiative transitions. These molecular interactions promote the manifestation of room-temperature phosphorescence. Furthermore, leveraging the superior luminescent properties of 3Fmo, the compound was successfully utilized in cellular imaging, where it achieved excellent imaging results, showcasing its potential for biomedical applications.

10.
Cardiol Res ; 15(5): 404-414, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39420979

RESUMO

Background: Previous investigations have established the anti-inflammatory properties of fibroblast growth factor 21 (FGF21). However, the specific mechanism through which FGF21 mitigates myocardial ischemia/reperfusion (I/R) injury by inhibiting neutrophil extracellular traps (NETs) remains unclear. Methods: A mice model of myocardial I/R injury was induced, and myocardial tissue was stained with immunofluorescence to assess NETs. Serum NETs levels were quantified using a PicoGreen kit. In addition, the expression levels of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and FGF21 were evaluated by Wes fully automated protein blotting quantitative analysis system. Moreover, a hypoxia/reoxygenation (H/R) model was established using AMPK inhibitor and agonist pretreated H9c2 cells to further explore the relationship between FGF21 and AMPK. Results: Compared with the control group, serum NETs levels were significantly higher in I/R mice, and a large number of NETs were formed in myocardial tissues (97.63 ± 11.45 vs. 69.65 ± 3.33, P < 0.05). However, NETs levels were reversed in FGF21 pretreated mice (P < 0.05). Further studies showed that FGF21 enhanced AMPK expression, which was significantly increased after inhibition of AMPK and decreased after promotion of AMPK (P < 0.05). Conclusions: FGF21 may exert cardioprotective effects by inhibiting I/R injury-induced NETs via AMPK.

11.
Signal Transduct Target Ther ; 9(1): 275, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39419977

RESUMO

PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, the efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into their action sites. Herein, based on the ultra-pH-sensitive and enzyme-sensitive nanotechnology, a type of polymer PROTAC conjugated and pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following the construction of the PROTAC for Cyclin-dependent kinase 4 and 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds to many treatments even immune checkpoint blockades was selected as the tumor model in this study. As a result, PSRNs were found to maintain nanostructure (40 nm) in circulation and efficiently accumulated in tumors via enhanced permeation and retention effect. Then, they were dissociated into unimers (<10 nm) in response to an acidic tumor microenvironment, facilitating tumor penetration and cellular internalization. Eventually, the CDK4/6 degrading PROTACs were released intracellularly following the cleavage of cathepsin B. Importantly, PSRNs led to the enhanced degradation of target protein in vitro and in vivo. The degradation of CDK4/6 also augmented the efficacy of immune checkpoint blockades, through the upregulation of programmed cell death-ligand 1 (PD-L1) expression in cancer cells and the suppression of regulatory T cells cell proliferation in tumor microenvironment. By combination with α-PD-1, an enhanced anti-tumor outcome is well achieved in CT26 tumor model. Overall, our study verifies the significance of precise intracellular delivery of PROTACs and introduces a promising therapeutic strategy for the targeted combination treatment of CRC.


Assuntos
Neoplasias Colorretais , Quinase 4 Dependente de Ciclina , Nanopartículas , Proteólise , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Humanos , Camundongos , Animais , Nanopartículas/química , Proteólise/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/genética , Catepsina B/metabolismo , Catepsina B/genética , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Am J Ophthalmol ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39424029

RESUMO

PURPOSE: To evaluate the effectiveness and safety of RLRL in delaying the progression of high myopes -6.00 D or worse. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. PARTICIPANTS: Two hundred and two high myopic children aged 7 to 12 years with cycloplegia spherical equivalent refraction (SE) ≤ -6.00 D, astigmatism less than 2.50 D, anisometropia of 1.50 D or less were enrolled from March 2022 to December 2022. Follow-up was completed in December 2023. METHODS: Eligible participants were randomly allocated to either the intervention (RLRL + single vision spectacle [SVS]) or the control group (SVS). The RLRL treatment was administered every day for 3 minutes, twice a day, with an interval of at least 4 hours. MAIN OUTCOMES MEASURES: The primary outcome was the change in axial length (AL) at 12 months compared to baseline. Secondary outcomes included changes in SE, changes of choroidal thickness (ChT) and retinal thickness (RT) in different circle sectors. Outcomes were analyzed by means of intention-to-treat and per-protocol methods. RESULTS: After 12-month treatment, AL and SE changes were -0.11 ± 0.25 mm and 0.18 ± 0.63 D for RLRL group and 0.32 ± 0.09 mm and -0.80 ± 0.42 D for control group. Axial shortening > 0.05 mm was observed to 59% in the RLRL and 0% in the control group at 12 months. ChT and RT from a single center were analyzed. In the RLRL group, ChT were thickened in all sectors at 12 months. RT was increased in parafoveal and perifoveal circles. In the control group, all sectors of ChT and only perifoveal RT were significantly thinner at 12 months. The multivariate linear regression model revealed significant correlations between changes in ChT central foveal circle and RT perifoveal circle at 1 month and AL changes at 12 months. No fundus structure changes, afterimage exceeding 6 minutes nor best corrected visual acuity decreased reported. CONCLUSIONS: RLRL could effectively shorten the AL and inhibit the progression of myopia in high myopic patients -6.00 D or worse. AL shortening is sustained over 12 months of treatment. These observed changes appeared to be associated with increases in ChT and RT.

13.
Ecotoxicol Environ Saf ; 286: 117144, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39418720

RESUMO

BACKGROUND: Diminished ovarian reserve (DOR), a triggering factor for female infertility, affects 10% ∼ 35% of women of reproductive age. It is still unclear whether exposure to toxic metals (including metalloid) is associated with DOR risk, especially with respect to their relationships with the clinical phenotypes of DOR. METHODS: A case-control study including 439 patients was conducted, and Ba, Ni, As, Tl, Cd, Pb, Hg, Al and Cr levels in BL and FF were measured. Subsequent analyses were focused on Ba, Ni, As and Tl, which had the highest weights in the associations of the nine toxic metals (including metalloid) with DOR risk, by integrating weighted quantile sum (WQS) regression and bayesian kernel machine regression (BKMR) models. Conditional logistic regression models and BKMR models were used to assess the individual and combined effects of Ba, Ni, As and Tl exposures on DOR risk. Multiple linear regression models were used to investigate the relationships between toxic metal (including metalloid) levels in BL and FF and the clinical characteristics of DOR. RESULTS: The levels of Ba [second vs. lowest tertile: adjusted odds ratio (aOR) and 95 % confidence interval (CI) = 1.97 (1.13, 3.44); highest vs. lowest tertile: aOR (95 % CI) = 2.38 (1.32, 4.26)], Ni [highest vs. lowest tertile: aOR (95 % CI) = 2.59 (1.45, 4.65)] and As [highest vs. lowest tertile: aOR (95 % CI) = 1.96 (1.18, 3.25)] in BL, and Ba [highest vs. lowest tertile: aOR (95 % CI) = 4.60 (1.68, 12.61)] in FF were significantly associated with a higher risk of DOR, respectively. The significantly positive combined effect of the four toxic metals (including metalloid) on DOR risk was exhibited when their BL levels exceeded the 25th percentile compared with their median levels. Among these, As (0.9822) and Ba (0.9704) were the primary contributors to this relationship. Similarly, this finding was confirmed by the statistical results from FF samples, with a linear positive correlation between combined exposure and DOR risk, where Ba (0.9440) was the primary contributor. Finally, elevated levels of Ba, Ni, and As in BL and Ba in FF were significantly linked to the higher follicle-stimulating hormone (FSH) levels. The levels of Ba in BL and FF, as well as As in BL, were significantly associated with the lower luteinizing hormone (LH)/FSH ratio values. CONCLUSION: Overall, the results of this study indicate that elevated levels of Ba, Ni, As and Tl are associated with a higher risk of DOR, whether individually or in combination, and that Ba levels in BL and FF are stable contributors. In addition, exposure to Ba, Ni, As and Tl is linked to various clinical phenotype parameters of DOR. Further research is needed to confirm these associations and to identify potential mechanisms involved.

14.
Biochem Genet ; 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39419909

RESUMO

Early diagnosis of cervicitis is important. Previous studies have found that neutrophil extracellular traps (NETs) play pro-inflammatory and anti-inflammatory roles in many diseases, suggesting that they may be involved in the inflammation of the uterine cervix and NETs-related genes may serve as biomarkers of cervicitis. However, what NETs-related genes are associated with cervicitis remains to be determined. Transcriptome analysis was performed using samples of exfoliated cervical cells from 15 patients with cervicitis and 15 patients without cervicitis as the control group. First, the intersection of differentially expressed genes (DEGs) and neutrophil extracellular trap-related genes (NETRGs) were taken to obtain genes, followed by functional enrichment analysis. We obtained hub genes through two machine learning algorithms. We then performed Artificial Neural Network (ANN) and nomogram construction, confusion matrix, receiver operating characteristic (ROC), gene set enrichment analysis (GSEA), and immune cell infiltration analysis. Moreover, we constructed ceRNA network, mRNA-transcription factor (TF) network, and hub genes-drug network. We obtained 19 intersecting genes by intersecting 1398 DEGs and 136 NETRGs. 5 hub genes were obtained through 2 machine learning algorithms, namely PKM, ATG7, CTSG, RIPK3, and ENO1. Confusion matrix and ROC curve evaluation ANN model showed high accuracy and stability. A nomogram containing the 5 hub genes was established to assess the disease rate in patients. The correlation analysis revealed that the expression of ATG7 was synergistic with RIPK3. The GSEA showed that most of the hub genes were related to ECM receptor interactions. It was predicted that the ceRNA network contained 2 hub genes, 3 targeted miRNAs, and 27 targeted lnRNAs, and that 5 mRNAs were regulated by 28 TFs. In addition, 36 small molecule drugs that target hub genes may improve the treatment of cervicitis. In this study, five hub genes (PKM, ATG7, CTSG, RIPK3, ENO1) provided new directions for the diagnosis and treatment of patients with cervicitis.

15.
Drug Metab Pharmacokinet ; 59: 101030, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39442386

RESUMO

Jaktinib is a novel Janus kinase (JAK) inhibitor, and a phase I clinical trial of single-dose Jaktinib was conducted in a population of subjects with hepatic impairment to assess the safety, tolerability, and pharmacokinetic characteristics of Jaktinib. The patients were administered orally with 100 mg Jaktinib on day 1 in all the mild hepatic impairment group (mild group, n = 8), moderate hepatic impairment group (moderate group, n = 8) and normal hepatic function group (normal group, n = 8), and the blood samples were collected for later analysis. The mild to moderate hepatic impairment affected the metabolism of Jaktinib, which may lead to accumulation of original Jaktinib. The pharmacokinetic characteristics of the metabolites (ZG0244 and ZG0245) of Jaktinib were also analyzed. The exposure of Jaktinib is approximately 2-fold in patients with mild and moderate hepatic impairment than normal hepatic function. No serious adverse events occurred. In summary, a dosage reduction is recommended for patients with mild or moderate hepatic impairment. Further investigations for the dose adjustment in mild/moderate hepatic impairment will be considered. Trial registration number: NCT04993404.

16.
Sci Adv ; 10(43): eadq2072, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39441939

RESUMO

Ex vivo or in vivo cell-hitchhiking has emerged as a potential means for efficient drug delivery and various disease therapies. However, many challenges remain, such as the complicated engineering process and dependence on ligand-receptor interaction. Here, we present a simple in vivo platelet-hitchhiking strategy based on self-assembling peptides without ligand modification. The engineered peptide nanofibers can hitchhike ultrafast (<5 s) and efficiently on both resting and activated platelets in a receptor-independent and species-independent manner. Mechanistic studies showed that unique secondary structure of nanofibers, which lead to surface exposure of hydrophobic and hydrogen bond-forming groups, might primarily contribute to the selective and efficient platelet-hitchhiking behavior. After intravenous injection, these peptide nanofibers hitchhiked in situ on circulating platelets and achieved almost 20-fold lung accumulation. Our study provides not only a different paradigm of in vivo platelet-hitchhiking beyond ligand-receptor recognition but also a potential strategy for lung-targeted drug delivery and pulmonary disease therapy.


Assuntos
Plaquetas , Nanofibras , Peptídeos , Nanofibras/química , Plaquetas/metabolismo , Peptídeos/química , Animais , Ligantes , Humanos , Camundongos , Ativação Plaquetária/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Engenharia de Proteínas/métodos , Agregação Plaquetária/efeitos dos fármacos
17.
J Phys Chem Lett ; 15(42): 10442-10450, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39388532

RESUMO

Terahertz (THz) coherent phonons have emerged as promising candidates for the next generation of high-speed, low-energy information carriers in atomically thin phononic or phonon-integrated on-chip devices. However, effectively manipulating THz coherent phonons remains a significant challenge. In this study, we investigated THz coherent phonon generation in exfoliated van der Waals (vdW) flakes of Fe3GeTe2, Fe5GeTe2, and FePS3. We successfully generated the THz A1g coherent phonon mode in these vdW flakes. An innovative approach involved partially exfoliating vdW flakes on a gold substrate and partially on a silicon (Si) substrate to compare the THz coherent phonon generation between both sides. Interestingly, we observed a significantly enhanced THz coherent phonon in the vdW/gold area compared with that in the vdW/Si area. Frequency-domain Raman mapping across the vdW flakes corroborated these findings. Numerical simulations further indicated a stronger enhanced surface field in vdW/gold structures than in vdW/Si structures. Consequently, we attribute the observed enhancement in THz coherent phonon generation to the increased surface field on the gold substrate. This enhancement was consistent across the three different vdW materials studied, suggesting the universality of this strategy. Our results hold promise for advancing the design of THz phononic and phonon-integrated devices.

18.
Chem Sci ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39360009

RESUMO

Fungal phytotoxins cause significant harm to agricultural production or lead to plant diseases. Discovering new phytotoxins, dissecting their formation mechanism and understanding their action mode are important for controlling the harmful effects of fungal phytopathogens. In this study, a long-term unsolved cluster (polyketide synthase 16, PKS16 cluster) from Fusarium species was thoroughly investigated and a series of new metabolites including both complex α-pyrone-polyketide glycosides and simple polyketide carboxylates were identified from F. proliferatum. The whole pathway reveals an unusual assembly and inactivation process for phytotoxin biosynthesis, with key points as follows: (1) a flavin dependent monooxygenase catalyzes Baeyer-Villiger oxidation on the linear polyketide side chain of α-pyrone-polyketide glycoside 8 to form ester bond compound 1; (2) a ß-glucosidase unexpectedly mediates the ester bond hydrolysis of 1 to generate polyketide carboxylate phytotoxin 2; (3) oxidation occurring on the terminal inert carbons of 2 by intracellular oxidase(s) eliminates its phytotoxicity. Our work identifies the chemical basis of the PKS16 cluster in phytotoxicity, shows that polyketide carboxylate is a new structural type of phytotoxin in Fusarium and importantly uncovers a rare ester bond hydrolysis function of ß-glucosidase family enzymes.

19.
Gastroenterol Nurs ; 47(5): 338-348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39356121

RESUMO

This study investigates the role of self-perceived burden as a mediating factor in the association between perceived partner responsiveness and fertility intentions in women of reproductive age diagnosed with inflammatory bowel disease. A sample of 366 female inflammatory bowel disease patients from Changsha, China, was recruited using convenience sampling. Participants completed assessments, including the Impact of Perceived Partner Responsiveness Scale, Self-Perceived Burden Scale, Fertility Intentions Questionnaire, and a demographic questionnaire. Results indicated a moderate-to-low level of fertility intentions (mean score: 5.33 ± 2.21), with corresponding moderate levels of self-perceived burden (mean score: 30.01 ± 10.02) and perceived partner responsiveness (mean score: 52.80 ± 17.03). Positive correlations were observed between perceived partner responsiveness and fertility intentions and negative correlations between self-perceived burden and fertility intentions. The relationship between perceived partner responsiveness and fertility intentions was found to be partially mediated by self-perceived burden. These findings highlight the significance of perceived partner responsiveness and self-perceived burden in shaping fertility intentions among women with inflammatory bowel disease.


Assuntos
Doenças Inflamatórias Intestinais , Intenção , Humanos , Feminino , Adulto , Doenças Inflamatórias Intestinais/psicologia , Adulto Jovem , Fertilidade , Autoimagem , Inquéritos e Questionários , China , Efeitos Psicossociais da Doença , Pessoa de Meia-Idade , Parceiros Sexuais/psicologia , Estudos Transversais
20.
Waste Manag ; 190: 251-260, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39357305

RESUMO

Rapid characterization of solid waste using near-infrared hyperspectral imaging (HSI) coupled with machine learning models has been increasingly investigated to replace the traditional time- and labor-intensive methods. However, contamination by waste-derived leachates or other fractions etc., can cause the spectra evolutions and significantly influences the identification performance, which has not been investigated before. The first attempt was made by using hyperspectral unmixing (HU) to extract the endmember components and demonstrate their contributions (abundance) to solid waste, taking the non-linear reflectance changes due to the O-H vibration of water and unclear variation associated with oil and leachates as an example. The HSI spectra of various solid waste components influenced by pure water, oil and three kinds of leachates were acquired. A novel method based on HU models, including multivariate curve resolution with alternating least squares and state-of-the-art autoencoder architectures (deep learning models), was developed to estimate the spectra of endmembers as well as their abundances in individual pixel. Their spatial distribution overview in solid waste was then yielded. The selected models were validated via an independent test data set, with lower spectral angle distance, 12.3° ± 6.5°, indicating the similarity of the predicted endmembers with real components. And the lowest root of mean square error on endmember distribution maps was 0.17. The non-linear liquid's effects by water and oil on spectra variations of solid waste were clearly illuminated. Additionally, the proposed method can extract information from mixed spectroscopic images and generate reconstructed spectra.

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