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1.
J Am Chem Soc ; 146(38): 26131-26138, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39276081

RESUMEN

Creating nanomachines capable of precisely capturing, organizing, and regulating the activity of target biomolecules holds profound significance for advancing nanotechnology and therapeutics. Here, we develop a multistage reconfigurable DNA nanocage that can enclose and modulate proteins through multivalent interactions, activated by specific molecular signals. By strategically designing and manipulating the strut architecture of the DNA nanocages, we can achieve precise control over their reconfiguration among pyramid, square, and linear branch shapes. Additionally, we demonstrated its ability to capture thrombin and effectively inhibit its coagulation activity by incorporating two thrombin-targeting aptamers into the designed arms of the DNA nanocage. The activity of thrombin can be recovered by rearranging the conformation of the DNA nanocage and exposing the protein, thereby activating the coagulation process. This approach enriches the design toolbox for dynamic nanomachines and inspires a new strategy for protein encapsulation and regulation with potential future therapeutic applications.


Asunto(s)
Aptámeros de Nucleótidos , ADN , Nanoestructuras , Trombina , Trombina/química , Trombina/metabolismo , ADN/química , Nanoestructuras/química , Aptámeros de Nucleótidos/química , Nanotecnología/métodos , Humanos
2.
Acad Radiol ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278760

RESUMEN

RATIONALE AND OBJECTIVES: Hepatocellular carcinoma (HCC) with invasion into the inferior vena cava (IVC) or the right atrium (RA) presents significant therapeutic challenges due to its rapid progression and limited available treatments. MATERIALS AND METHODS: This retrospective study evaluated the effectiveness of hepatic arterial infusion chemotherapy alongside lenvatinib and PD-1 inhibitors (HAIC-Len-PD1) compared to treatment with only lenvatinib and PD-1 inhibitors (Len-PD1). A total of 115 patients with HCC and IVC or RA invasion were included. We analyzed groups for median overall survival (OS) and progression-free survival (PFS) through the Kaplan-Meier method, along with tumor response rates, disease control rates, and adverse event frequencies. RESULTS: The HAIC-Len-PD1 treatment showed a marked improvement in median OS (22.2 vs. 14.4 months; P = 0.007) and median PFS (13.8 vs. 5.1 months; P = 0.001) over the Len-PD1 regimen. There was also a higher overall response rate (68.7% vs. 37.5%; P < 0.05) and disease control rate (92.5% vs. 75%; P < 0.05) observed in the HAIC-Len-PD1 group. A subgroup analysis demonstrated consistent survival benefits across diverse patient demographics. Although the incidence of adverse events was higher in the HAIC-Len-PD1 group, these were generally manageable and well-tolerated. CONCLUSION: The combined regimen of HAIC, lenvatinib, and PD-1 inhibitors may improve survival and tumor management in HCC patients with IVC or RA invasion, suggesting a potential therapeutic option for this critically at-risk group. Further research in the form of randomized controlled trials are needed to verify these findings for advanced-stage HCC with vascular compromise.

3.
Sci Rep ; 14(1): 22133, 2024 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333782

RESUMEN

Patients with stage IIB/C (T4a-bN0) colon cancer often exhibit worse survival rates compared to those with stage IIIA (T1-2N1, T1N2a) colon cancer. This study re-evaluates the survival paradox using the latest Surveillance, Epidemiology, and End Results (SEER) data (released on April 17, 2024) to inform potential revisions to the staging criteria. Utilizing SEER data with 8th edition TNM staging criteria, 4692 colon cancer patients diagnosed between 2018 and 2021 were analyzed with chi-square test. Cox regression and Kaplan-Meier survival analysis were employed to assess factors associated with cancer-specific survival (CSS) and overall survival (OS). The 3-year CSS rates for stage IIB and IIC were 73.1% and 70.3%, respectively, whereas stage IIIA had a substantially higher CSS rate of 91% (P < 0.001). Similarly, the OS rates were 64.9% and 63.0% for stage IIB and IIC, respectively, compared to 83.1% for stage IIIA (P < 0.001). Multivariate analyses revealed stage IIIA patients had significantly lower risks of cancer-specific mortality (hazard ratio (HR) = 0.374, 95% CI: 0.296-0.473, P < 0.001) and overall mortality (HR = 0.575, 95% CI: 0.483-0.685, P < 0.001) compared to stage IIB patients. The upcoming 9th edition of the AJCC staging system should address this paradox by integrating advanced diagnostic markers and emphasizing the aggressive biology of T4 tumor, providing more accurate prognostic information and guiding more effective treatment strategies for colon cancer patients.


Asunto(s)
Neoplasias del Colon , Estadificación de Neoplasias , Programa de VERF , Humanos , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Estimación de Kaplan-Meier , Pronóstico , Adulto , Modelos de Riesgos Proporcionales , Anciano de 80 o más Años
4.
Hepatobiliary Surg Nutr ; 13(4): 616-631, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39175713

RESUMEN

Background: Hepatocellular carcinoma (HCC) treatment currently lacks adjuvant therapy with a high level of supporting evidence to reduce recurrence after hepatectomy. This study aimed to assess the safety and efficacy of camrelizumab plus apatinib in the adjuvant therapy of patients with HCC with microvascular invasion (MVI). Methods: Data were retrospectively collected on consecutive patients with HCC who underwent radical resection and were diagnosed with MVI-positive tumors between October 2019 and June 2022 at four centers. The association between adjuvant therapy and prognosis [recurrence-free survival (RFS), overall survival (OS)] was evaluated by propensity score matching (PSM), the log-rank test, Cox regression analysis, and subgroup analysis. Furthermore, grade 3 or 4 treatment-related adverse events (TRAEs) of adjuvant therapy were reported. Results: Among the 111 patients in the adjuvant therapy group and 276 patients in the observation group at enrolment, there were 99 and 172 in the adjuvant therapy and observation groups after PSM, respectively. RFS was better in the adjuvant therapy group [hazard ratio (HR) 0.52; 95% confidence interval (CI): 0.39 to 0.69; P<0.001], whereas OS was not (HR 0.62; 95% CI: 0.39 to 0.99; P=0.079). These results were confirmed after PSM. Subgroup analyses were generally consistent in favour of adjuvant camrelizumab plus apatinib with better RFS. Grade 3 or 4 TRAEs accounted for 20.7% during adjuvant therapy; the most common TRAEs included hypertension and proteinuria. Conclusions: Postoperative adjuvant camrelizumab plus apatinib significantly improved the RFS benefits with acceptable toxicities in patients with HCC with MVI.

5.
Arthrosc Tech ; 13(6): 102970, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39036396

RESUMEN

Injuries of the posterior root of the medial meniscus can be accompanied by damage to the anterior cruciate ligament or often occur independently in cases of degenerative meniscal injury in older individuals. Anchor suture repair can achieve favorable biomechanical effects and clinical outcomes. However, anchor placement is technically challenging and requires a posterior medial approach, which increases the risk of iatrogenic injury. To address these issues, we have utilized the reverse anchor technique to repair the posterior root of the medial meniscus. This technique offers advantages such as reduced surgical time, simplified operation, and reduced risk of the "bungee effect" and iatrogenic injury.

6.
PLoS One ; 19(7): e0307269, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39018284

RESUMEN

Urtica cannabina L. (UL) has been used clinically for centuries because of its anti-inflammatory properties. This study aimed to investigate the underlying mechanisms and anti-inflammatory effects of different UL concentrations in zebrafish. To elucidate UL's anti-inflammatory properties, two inflammation zebrafish models were designed 1) by severing the zebrafish's caudal fin to assess the repairing effect of UL on the tail inflammation, and 2) by inducing lipopolysaccharides (LPS)-mediated intestinal inflammation to assess the protective and reparative effects of UL on intestinal inflammation at the histological and genetic levels. Furthermore, the effect of UL on the LPS-induced intestinal flora changes was also assessed. After caudal fin resection, a scar formed on the tail of the zebrafish, and the area of the caudal fin increased by 1.30 times as much as that of the control group (P < 0.01). Moreover, this tail scar was alleviated after 10 mg/g UL supplementation but not after 30 mg/g UL dose. LPS decreased the feed intake and body weight of the zebrafish; however, these effects were reversed after 10 and 30 mg/g doses of UL. In addition, the LPS treatment also reduced the intestinal goblet cells by 49% in the zebrafish when compared with the control, which was significantly restored after 10 and 30 mg/g UL treatments. At the genetics level, the expression of the pro-inflammatory cytokine genes (TNF-α, IL6, and IL8) showed that 10 and 30 mg/g UL doses could rescue LPS-induced expression. The gut microbiota analysis revealed changes in the abundance of four major bacterial phyla in the 10 and 30 mg/g UL-treated groups, with an increased probiotic Bacteroidota and decreased pathogenic bacteria. These results indicate that UL strongly inhibits inflammation caused by caudal fin removal and LPS-induced inflammatory changes in the zebrafish intensity, suggesting that UL is a feed additive that could be developed to improve resistance to inflammation in livestock.


Asunto(s)
Antiinflamatorios , Lipopolisacáridos , Pez Cebra , Animales , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Microbioma Gastrointestinal/efectos de los fármacos , Aditivos Alimentarios/farmacología , Alimentación Animal , Extractos Vegetales/farmacología
7.
J Bone Miner Metab ; 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39069602

RESUMEN

INTRODUCTION: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women. MATERIALS AND METHODS: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs. RESULTS: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test). CONCLUSION: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs.

8.
Int J Transgend Health ; 25(3): 471-482, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055628

RESUMEN

Objective: Cyproterone acetate (CPA) and spironolactone (SPL) are different antiandrogens in gender-affirming hormone therapy (GAHT) for transgender women. Few studies have evaluated their efficacy and user satisfaction, especially among East Asians. This study aimed to evaluate these aspects in Chinese transgender women. Methods: Data were collected retrospectively from transgender women visiting the Peking University Third Hospital from 2012 to 2021. From 639 people identified as transgender women, 151 of them (80 using CPA and 71 using SPL, 16 to 40-year-old) under stable GAHT ≥6 months were enrolled. Total testosterone levels and visual analogue scale (VAS)-based satisfaction scores were evaluated. Results: No difference was observed in age between the CPA and SPL groups (median [IQR], 22 [20-24] years and 23 [20-26] years, respectively). The duration of GAHT was longer in CPA group than in SPL group (18 [10-32] months vs. 12 [8-21] months, p = 0.009). Total testosterone levels were significantly lower with CPA treatment (25 mg/d) than with SPL treatment (100 mg/d) (median [IQR]: 0.7 [0.7-2.1] nmol/L vs. 13.0 [6.0-17.8] nmol/L, p < 0.001). The proportion of total testosterone levels reaching the recommended range was significantly higher in CPA group than in SPL group (75.0% vs. 11.3%, p < 0.001). VAS-based satisfaction scores for erection decreased and figure feminization were higher in CPA group than in SPL group, which remained unchanged after adjusting for age, treatment duration, estradiol dose, and comorbid mental disorders (p < 0.05). The prolactin levels were higher in CPA group than in SPL group (18.9 [11.8-28.1] ng/ml vs. 11.8 [7.9-18.4] ng/ml, p < 0.001). No severe safety events were reported in both groups. Conclusion: In Chinese transgender women, CPA was more effective than SPL in lowering testosterone levels. Additionally, VAS scores indicated greater satisfaction with erection decreased and figure feminization using CPA compared to SPL.

9.
BMC Cancer ; 24(1): 922, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080642

RESUMEN

Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Progresión de la Enfermedad , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Factor de Transcripción STAT1 , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/inmunología , Quinolinas/farmacología , Quinolinas/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/inmunología , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Factor de Transcripción STAT1/metabolismo , Animales , Ratones , Humanos , Proliferación Celular/efectos de los fármacos , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Masculino , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología
10.
Cancer Med ; 13(12): e7410, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38923354

RESUMEN

BACKGROUND: The CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib. METHODS: This retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression-free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort. RESULTS: We included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p < 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p < 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS. CONCLUSIONS: The CRAFITY score, utilizing C-reactive protein and alpha-fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Quimioembolización Terapéutica/métodos , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Pronóstico , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Adulto
11.
Colloids Surf B Biointerfaces ; 239: 113962, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38749167

RESUMEN

The undesirable and inevitable adhesion of marine organisms on submerged surfaces has seriously affect the environment, economy and society, so emerging and promising strategies for antifouling are required. Here, the novel and environmental strategy of the antibacterial and antialgal materials was proposed for the application of the antifouling coating without releasing harmful substances. The environment-friendly antifouling agent, the capsaicin derivative N-(2,5-dihydroxy-4-acrylamide meth-ylbenzyl)acrylamide (PHABA), was modified to the molecular chain of the polyurethane. The best tensile strength was up to 23.5 MPa of PUP-25% and the elongation at break was 415% of PUP-25%. The excellent wear resistance (300 wear cycles) and chemical solution resistance (H2SO4, NaOH, and NaCl solutions) revealed the applicability of the coating. PHABA would migrate to the surface of the polyurethane coating with time and enhanced the antibacterial and antialgal properties of the coating. PUP-25% prevented more than 90% of bacterial and algal adhesion, indicating the potential application of the antifouling coating.


Asunto(s)
Antibacterianos , Poliuretanos , Propiedades de Superficie , Poliuretanos/química , Poliuretanos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Hidroquinonas/química , Hidroquinonas/farmacología , Pruebas de Sensibilidad Microbiana , Adhesión Bacteriana/efectos de los fármacos , Incrustaciones Biológicas/prevención & control , Acrilamida/química , Acrilamida/farmacología , Resistencia a la Tracción
12.
J Environ Manage ; 361: 121258, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38815428

RESUMEN

The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.


Asunto(s)
Biodegradación Ambiental , Poliésteres , Tereftalatos Polietilenos , Tereftalatos Polietilenos/química , Tereftalatos Polietilenos/metabolismo , Poliésteres/metabolismo , Poliésteres/química , Hidrolasas de Éster Carboxílico
13.
BMC Cancer ; 24(1): 480, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627684

RESUMEN

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable. CONCLUSION: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Estudios Retrospectivos , Neoplasias Hepáticas/tratamiento farmacológico
14.
Artículo en Inglés | MEDLINE | ID: mdl-38447648

RESUMEN

Gelsemium elegans (GE), also known as Duanchangcao, is a plant associated with toxic symptoms related to the abdomen; however, the toxicity caused by GE remains unknown. Gelsemine (GEL) is an alkaloid extracted from GE and is one of the most toxic alkaloids. This study used zebrafish as an animal model and employed high-throughput gene sequencing to identify genes and signaling pathways related to GEL toxicity. Exposure to GEL negatively impacted heart rate, swim bladder development, and activity in zebrafish larvae. Transcriptomics data revealed the enrichment of inflammatory and phagocyte signaling pathways. RT-PCR analysis revealed a decrease in the expression of pancreas-related genes, including the pancreatic coagulation protease (Ctr) family, such as Ctrl, Ctrb 1, and Ctrc, due to GEL exposure. Furthermore, GEL exposure significantly reduced Ctrb1 protein expression while elevating trypsin and serum amylase activities in zebrafish larvae. GEL also resulted in a decrease in pancreas-associated fluorescence area and an increase in neutrophil-related fluorescence area in transgenic zebrafish. This study revealed that GEL toxicity in zebrafish larvae is related to acute pancreatic inflammation.


Asunto(s)
Alcaloides , Gelsemium , Animales , Pez Cebra/metabolismo , Gelsemium/metabolismo , Larva/metabolismo
15.
Phys Rev Lett ; 132(6): 060602, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38394561

RESUMEN

The fluxonium qubits have emerged as a promising platform for gate-based quantum information processing. However, their extraordinary protection against charge fluctuations comes at a cost: when coupled capacitively, the qubit-qubit interactions are restricted to XX interactions. Consequently, effective ZZ or XZ interactions are only constructed either by temporarily populating higher-energy states, or by exploiting perturbative effects under microwave driving. Instead, we propose and demonstrate an inductive coupling scheme, which offers a wide selection of native qubit-qubit interactions for fluxonium. In particular, we leverage a built-in, flux-controlled ZZ interaction to perform qubit entanglement. To combat the increased flux-noise-induced dephasing away from the flux-insensitive position, we use a continuous version of the dynamical decoupling scheme to perform noise filtering. Combining these, we demonstrate a 20 ns controlled-z gate with a mean fidelity of 99.53%. More than confirming the efficacy of our gate scheme, this high-fidelity result also reveals a promising but rarely explored parameter space uniquely suitable for gate operations between fluxonium qubits.

16.
Photobiomodul Photomed Laser Surg ; 42(3): 230-237, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38417045

RESUMEN

Objective: To evaluate the therapeutic effect of a novel air-cooled Nd:YAG laser in the venous lakes of the lips (VLL). Background: The thermal injury is one of the most important issues during laser therapy for venous lakes. Methods: Six pieces of fresh pork livers were used to provide 30 regions with a diameter of 6 mm for experiment in vitro, among which 15 regions were treated by Nd:YAG laser with air cooling until the tissue turned gray-white, whereas the rest were treated without air cooling as control. The operation time of laser irradiation, the degree of temperature increase, and the depth of coagulation tissue were compared between two groups. Then, 60 VLL patients were selected for Nd:YAG laser treatment with or without air cooling. The operation time of laser irradiation, the degree of temperature increase, the postoperative pain visual analog scale (VAS) score, and the percentage of lesions removed within 1 month were compared. Results: In tissue studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and there was no significant statistical difference in the depth of coagulation tissue (p = 0.624). In clinical studies, the treated group showed a longer operation time of laser irradiation (p < 0.01), a lower degree of temperature increase (p < 0.01), and a lower VAS score on the 1st and 2nd day, compared with the control group (p < 0.01). Conclusions: Air cooling during Nd:YAG laser for the treatment of VLL can prolong the surgical time, but lowered tissue temperature and reduced patient pain within 2 days under the premise of ensuring the treatment effect.


Asunto(s)
Terapia por Láser , Láseres de Estado Sólido , Terapia por Luz de Baja Intensidad , Humanos , Láseres de Estado Sólido/uso terapéutico , Labio/cirugía , Temperatura
17.
Gene ; 908: 148289, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38360125

RESUMEN

BACKGROUND: Lupus nephritis (LN) is a type of autoimmune disease that impacts the kidneys. Exosomes are valuable for in-depth studies of the pathogenesis of LN. This study aimed to explore miR-181d-5p expression levels in M0 macrophage-derived exosomes and their role in human renal mesangial cells (HRMC) pyroptosis through binding to BCL-2. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from patients with lupus nephritis (LN) and healthy subjects. Monocytes isolated from these samples were induced into M0 macrophages using recombinant human granulocyte colony-stimulating factor (rhG-CSF). In a parallel process, THP-1 cells were induced into M0 macrophages using Phorbol Myristate Acetate (PMA). LPS- and ATP-stimulated HRMC were used to construct a cell pyroptosis model. We then introduced different miR-181d-5p mimic fragments into the M0 macrophages derived from the THP-1 cells. Subsequently, exosomes from these macrophages were co-cultured with HRMC. To evaluate the impact on HRMC, we conducted proliferation and apoptosis assessments using CellCountingKit-8assay and flow cytometry. The effect of exosomal miR-181d-5p on HRMC pyroptosis was assessed using western blot. The miR-181d-5p and BCL-2 targeting relationship was detected using real-time fluorescence quantitative PCR. IL-6, IL-1ß, and TNF-α levels in cell supernatants were detected using ELISA kits. RESULTS: In this study, we observed an increase in miR-181d-5p levels within exosomes secreted from M0 macrophages obtained by induction of monocytes from LN patients. It was found that miR-181d-5p can target binding to BCL-2. Exosomes with elevated levels of miR-181d-5p contributed to a significant increase in miR-181d-5p within HRMC, facilitating its proliferation and inhibiting apoptosis. Furthermore, exosomes expressing high levels of miR-181d-5p were observed to promote an inflammatory response and pyroptosis in HRMC. Notably, these effects were reversed when the levels of miR-181d-5p in the exosomes were reduced. CONCLUSION: Inhibition of miR-181d-5p, derived from M0 macrophage exosomes, effectively suppresses inflammation and pyroptosis in HRMC. This discovery indicates that miR-181d-5p holds the potential as a valuable target in the development of treatments for Lupus Nephritis (LN).


Asunto(s)
Exosomas , Nefritis Lúpica , MicroARNs , Humanos , Caspasa 1/genética , Células Mesangiales , Piroptosis/genética , Nefritis Lúpica/genética , Exosomas/genética , Leucocitos Mononucleares , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Macrófagos , MicroARNs/genética , Gasderminas , Proteínas de Unión a Fosfato
18.
Nanoscale ; 16(4): 1685-1691, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38193377

RESUMEN

DNA double-crossover motifs, including parallel and antiparallel crossovers, serve as the structural foundation for the creation of diverse nanostructures and dynamic devices in DNA nanotechnology. Parallel crossover motifs have unique advantages over the widely used antiparallel crossover design but have not developed as substantially due to the difficulties in assembly. Here we created 29 designs of parallel double-crossover motifs varying in hybridization pathways, central domain lengths, and crossover locations to investigate their assembly mechanism. Arrays were successfully formed in four distinct designs, and large tubular structures were obtained in seven designs with predefined pathways and central domains appoximately 16 nucleotides in length. The nanotubes obtained from parallel crossover design showed improved nuclease resistance than the ones from the antiparallel counterpart design. Overall, our study provides a basis for the development of generalized assembly rules of DNA parallel crossover systems and opens new opportunities for their potential use in biological systems.


Asunto(s)
Nanoestructuras , Nanotubos , Conformación de Ácido Nucleico , ADN/química , Nanotecnología , Nanoestructuras/química , Nanotubos/química
19.
Pain Physician ; 27(1): 59-67, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38285036

RESUMEN

BACKGROUND: Postoperative sacroiliac joint pain (SIJP) is a common manifestation of failed back surgery syndrome after a posterior lumbar interbody fusion (PLIF). However, there is currently no consensus on the risk factors for SIJP after PLIF. OBJECTIVES: We explored the effects of abdominal obesity and sagittal imbalance on SIJP after PLIF. STUDY DESIGN: This is a prospective observational cohort study. SETTING: This study occurred at the Department of Spinal Surgery at a hospital affiliated with a medical university. METHODS: A total of 401 patients who underwent PLIF from June 2018 to June 2021 were enrolled in this study. 36 patients experienced postoperative SIJP. In contrast, a matched group comprised 72 non-SIJP patients. We used 1:2 propensity score matching to compare obesity features and sagittal spine parameters in the 2 groups. Inflammatory cytokines and visual analog scale (VAS) scores were measured in the SIJP group. RESULTS: A total of 36 patients (8.98%) experienced SIJP during the follow-up. Compared with the non-SIJP group, patients with postoperative SIJP had a higher body mass index (BMI), greater abdominal obesity, a higher incidence of pelvic incidence-lumbar lordosis greater than 10°, and a higher incidence of a sagittal vertical axis greater than 5 cm (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve for waist circumference was greater than that for BMI (0.762 vs. 0.650, P = 0.049). Logistic regression analysis revealed that the risk factors for SIJP were abdominal obesity, a pelvic incidence-lumbar lordosis of greater than 10°, and a sagittal vertical axis greater than 5 cm (P < 0.05). In patients with SIJP, interleukin 6, tumor necrosis factor-α, and VAS scores were higher in the abdominal obesity group than in the non-abdominal obesity group (P < 0.05). LIMITATIONS: There was no uniform diagnosis of SIJP, so the incidence rate of SIJP might not be accurate. CONCLUSIONS: The significant predictors of SIJP were abdominal obesity and sagittal imbalance. Patients with abdominal obesity showed higher levels of inflammatory markers and pain intensity. More attention should be paid to body shape and the angle of correction of lumbar lordosis before lumbar surgery.


Asunto(s)
Lordosis , Obesidad Abdominal , Animales , Humanos , Obesidad Abdominal/complicaciones , Obesidad Abdominal/cirugía , Estudios de Cohortes , Articulación Sacroiliaca/cirugía , Obesidad , Dolor Pélvico , Artralgia
20.
Opt Express ; 32(1): 62-78, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38175063

RESUMEN

The Ritchey-Common test is widely adopted to measure large optical flats. The traditional Ritchey-Common test eliminates the defocus error with multiple tests by changing the position of the mirrors, which suffers from cumbersome steps, poor repeatability, coupled system error, extra mirror deformation, and potential overturning. The above problems increase the test time, decrease the reliability and accuracy, increase the test cost, and threaten manufacturing safety. We propose a single-test Ritchey-Common interferometry to avoid the obligatory position change in the traditional method. A sub-aperture of test flat is directly measured by a small-aperture interferometer before the test, which is easy to implement, to replace the extra system wavefront measurement in different positions. The defocus is calculated in sub-aperture at exactly the same position as the full-field measurement without the position change, then the surface form under test can be obtained with accurate optical path modeling. Measurement experiments for 100 mm and 2050 mm aperture flats were performed to demonstrate the feasibility of this method. Compared with a direct test in a standard Zygo interferometer, the peak to valley (PV) and root mean square (RMS) errors were 0.0889 λ and 0.0126 λ (λ=632.8 nm), respectively, which reaches the upper limit of accuracy of the interferometer. To the best of our knowledge, this is the first proposal of the Ritchey-Common test that can eliminate the defocus error and realize high accuracy measurement in a single test. Our work paves the way for reliable and practical optical metrology for large optical flats.

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