Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 193
Filtrar
1.
Polymers (Basel) ; 16(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39000758

RESUMEN

Silicone rubber (SR) is a kind of polymer insulation material with excellent performance. With the service life of silicone rubber products reaching the limit, how to dispose of waste silicone rubber is an urgent problem to be solved. In this paper, silicone rubber-modified asphalt binder (SRMA) was prepared by SR and 90# base asphalt binder. The simulated short-term aging and long-term aging tests of SRMA were carried out using the thin film oven aging test (TFOT) and pressure aging vessel test (PAV). The rotary viscosity test and dynamic shear rheological test (DSR) were applied to the rheological properties of SRMA before and after aging. The degradation degree and chemical composition changes of SR were explored by the toluene insoluble matter test, Fourier transform infrared spectroscopy (FTIR), and a Fluorescence microscope (FM). The results demonstrate that SR can significantly affect the aging resistance, fatigue life, and high-temperature stability of SRMA. As the content of SR rose, the elastic component in SRMA increased, leading to a nice performance in stability at high temperatures and fatigue resistance. However, excessive content (14%wt and 16%wt) had a negative influence on the performance of SRMA. So, the optimal content was speculated to be between 12% and 14%. Furthermore, SR and asphalt binder would be aged and degraded together in the aging process, and this phenomenon was more obvious during long-term aging.

2.
Life Sci ; : 122912, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39004272

RESUMEN

DNA damage causes genomic instability. To maintain genome integrity, cells have evolved DNA damage response, which is involved in replication fork disassembly and DNA replication termination. However, the mechanism underlying the regulation of replication fork disassembly and its connection with DNA damage repair remain elusive. The CMG-MCM7 subunit ubiquitination functions on the eukaryotic replication fork disassembly at replication termination. Until now, only ubiquitin ligases CUL2LRR1 have been reported catalyzing MCM7 ubiquitination in human cells. This study discovered that in human cells, the ubiquitin ligase RNF8 catalyzes K63-linked multi-ubiquitination of MCM7 at K145 both in vivo and in vitro. The multi-ubiquitination of MCM7 is dynamically regulated during the cell cycle, primarily presenting on chromatin during the late S phase. Additionally, MCM7 polyubiquitylation is promoted by RNF168 and BRCA1 during DNA replication termination. Upon DNA damage, the RNF8-mediated polyubiquitination of MCM7 decreased significantly during the late S phase. This study highlights the novel role of RNF8-catalyzed polyubiquitination of MCM7 in the regulation of replication fork disassembly in human cells and linking it to DNA damage response.

3.
BMC Cancer ; 24(1): 850, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020297

RESUMEN

BACKGROUND: This study was designed to evaluate the effect of progesterone receptor (PR) status on the prognosis of advanced estrogen receptor (ER)-high human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. METHODS: Advanced ER-high HER2-negative breast cancer patients who were admitted to Harbin Medical University Cancer Hospital and received cyclin-dependent kinase (CDK)4/6 inhibitor combined with endocrine as first-line therapy were included for analysis. Patients were divided into PR-high group (11-100%), PR-low group (1-10%), and PR-negative group (< 1%) according to the expression of PR. Chi-square test was used to analyze the correlation of variables between groups. COX regression analysis were used to analyze the risk factors of survival. Kaplan-Meier survival curve was used to analyze the differences of progression-free survival (PFS) and overall survival (OS) between groups. RESULTS: Among the 152 patients, 72 were PR-high, 32 were PR-low, and 48 were PR-negative. Compared with PR-negative group, the proportions of disease-free survival (DFS) ≥ 5 years and Ki-67 index ≤ 30% in PR-low group and PR-high group were significant higher. PR-negative patients were more likely to occur first-line progression of disease within 24 months (POD24) than PR-high(P = 0.026). Univariate and multivariate analysis showed that PR-negative and first-line POD24 occurrence were risk factors for survival. Survival curve analysis showed that compared with PR-high group, the PFS and OS were significantly lower in PR-negative group (P = 0.001, P = 0.036, respectively). Patients with first-line POD24 had shorter OS in the overall population as well as in subgroups stratified by PR status. CONCLUSIONS: PR-negative and first-line POD24 occurrence were risk factors of advanced ER-high HER2-negative breast cancer patients receiving CDK4/6 inhibitor combined with endocrine as first-line therapy. PR-negative patients had shortest PFS and OS. Regardless of PR status, first-line POD24 occurrence predicted shorter OS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Persona de Mediana Edad , Receptores de Estrógenos/metabolismo , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Pronóstico , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Estimación de Kaplan-Meier , Estudios Retrospectivos , Antineoplásicos Hormonales/uso terapéutico
4.
J Chem Inf Model ; 64(13): 5303-5316, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38921060

RESUMEN

The coexistence of amyloid-ß (Aß) and human islet amyloid polypeptide (hIAPP) in the brain and pancreas is associated with an increased risk of Alzheimer's disease (AD) and type 2 diabetes (T2D) due to their coaggregation and cross-seeding. Despite this, the molecular mechanisms underlying their interaction remain elusive. Here, we systematically investigated the cross-talk between Aß and hIAPP using atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that the amyloidogenic core regions of both Aß (Aß10-21 and Aß30-41) and hIAPP (hIAPP8-20 and hIAPP22-29), driving their self-aggregation, also exhibited a strong tendency for cross-interaction. This propensity led to the formation of ß-sheet-rich heterocomplexes, including potentially toxic ß-barrel oligomers. The formation of Aß and hIAPP heteroaggregates did not impede the recruitment of additional peptides to grow into larger aggregates. Our cross-seeding simulations demonstrated that both Aß and hIAPP fibrils could mutually act as seeds, assisting each other's monomers in converting into ß-sheets at the exposed fibril elongation ends. The amyloidogenic core regions of Aß and hIAPP, in both oligomeric and fibrillar states, exhibited the ability to recruit isolated peptides, thereby extending the ß-sheet edges, with limited sensitivity to the amino acid sequence. These findings suggest that targeting these regions by capping them with amyloid-resistant peptide drugs may hold potential as a therapeutic approach for addressing AD, T2D, and their copathologies.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Diabetes Mellitus Tipo 2 , Polipéptido Amiloide de los Islotes Pancreáticos , Simulación de Dinámica Molecular , Enfermedad de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Polipéptido Amiloide de los Islotes Pancreáticos/química , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Humanos , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/química , Agregado de Proteínas
5.
J Immunother Cancer ; 12(6)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38925680

RESUMEN

BACKGROUND: The majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S228P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc-Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc-Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks. METHODS: Trastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc-Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S228P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S228P-R409K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populations RESULTS: Experiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc-Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects. CONCLUSIONS: Fc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc-Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S228P-R409K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.


Asunto(s)
Inmunoglobulina G , Inmunoterapia , Inmunoglobulina G/inmunología , Animales , Ratones , Humanos , Inmunoterapia/métodos , Fragmentos Fc de Inmunoglobulinas/farmacología , Femenino , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo
6.
Int J Nanomedicine ; 19: 6035-6055, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911505

RESUMEN

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments. Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining. Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment. Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment.


Asunto(s)
Trastorno del Espectro Autista , Disfunción Cognitiva , Modelos Animales de Enfermedad , Proteína Doblecortina , Fulerenos , Ratones Endogámicos C57BL , Animales , Ratones , Fulerenos/farmacología , Fulerenos/química , Trastorno del Espectro Autista/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Masculino , Conducta Social , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/genética , Fármacos Neuroprotectores/farmacología , Neurogénesis/efectos de los fármacos , Trastorno Autístico/tratamiento farmacológico
7.
Clin Case Rep ; 12(6): e9031, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38883224

RESUMEN

Key Clinical Message: Acute chest pain can be the first manifestation of multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN). Comprehensive treatment may be an effective strategy for MEN1-associated NEN. Abstract: Multiple endocrine neoplasia type 1(MEN1)-associated thymic neuroendocrine neoplasms (NEN) is caused by the mutation of tumor suppressor MEN1 gene. Patients with MEN1-associated NEN initially presenting with acute chest pain are very rare. In the manuscript, we reported a case of a 45-year-old man who developed MEN1-associated NEN with acute chest pain as initial symptom. Thoracoscopic thymotomy was performed and thymic NEN was successfully removed. Genetic test showed a germline mutation of MEN1 gene in this patient. Immunohistochemical staining exhibited Syn(+), CgA(+), INSM1(+), CD56(+) and Ki67-positive cells (2%) in MEN1-associated NEN. Further evaluation unveiled MEN1-associated benign tumors including digestive NEN and pituitary gland adenoma. The 99mTc-HYNIC-TOC scintigraphy showed that focally increased radioactivity in the mid-upper abdomen. This patient was administered with 50Gy/25F of radiation dose to treat the postoperative lesions. Subsequently, sandostatin LAR (30 mg per week) was used as systemic therapy. He had no recurrence or metastasis for 6-month follow-up. Thus, acute chest pain can be the first manifestation of MEN1-associated NEN, and comprehensive treatment including surgery, radiation and systemic treatment may be an effective strategy for MEN1-associated NEN.

8.
Microsc Res Tech ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856633

RESUMEN

Rosa laxa Retz. is an unexplored Rosaceae plant in Xinjiang, China, and its flower is traditionally used in Kazak to treat the common cold, fever, and epileptic seizures and lessen the effects of aging. In the present study, the pharmacognostic profiles, physicochemical properties, phytochemical characteristics, and in vitro antioxidant potency of Rosa laxa Retz. flos (RLF) were presented. In the pharmacognostic evaluation of RLF, organoleptic characteristics, internal structures, and powder information were observed, and physicochemical parameters, including moisture content, ash, pH value, swelling degree, and extractives were examined. The quantitative analysis of the chemical composition of four different polar extracts of RLF showed that the aqueous part had the highest total triterpene acid, flavonoid, and polyphenol content (4.50 ± 0.04 mg/g, 50.56 ± 0.03 mg/g, and 60.20 ± 0.09 mg/g, respectively). A high-performance liquid chromatography (HPLC)-diode array detector (DAD) method was established and the contents of gallic acid, ellagic acid, astragalin, and tiliroside in RLF were determined simultaneously. In the set concentration range, the linear relationship among the four components was good (r > 0.999), the average recoveries were 97.36%-100.54%. The contents of gallic acid, ellagic acid, astragalin, and tiliroside in RLF samples were (9.46 ± 2.31) mg/g, (10.60 ±0.75) mg/g, (1.13 ± 2.50) mg/g, and (1.11 ± 2.65) mg/g, respectively. The types of its secondary metabolites were determined by fluorescence, color reaction by chemical solvent method, and ultraviolet-visible (UV-Vis) spectroscopy. The functional groups of its secondary metabolites were determined by Fourier transform infrared (FTIR) spectroscopy. Results showed that RLF contains a variety of secondary metabolic products, including flavonoids, phenolic acid, glycoside, and organic acid. TLC identification showed it contains ursolic acid, ß-sitosterol, tiliroside, astragalin, isoquercitrin, kaempferol-3-O-rutinoside, gallic acid, and ellagic acid. The in vitro antioxidant activity of different polar parts of RLF was investigated by DPPH, ABTS, and reduction performance experiments. The aqueous extract had the strongest antioxidant capacity, consistent with the high content of triterpene acids, flavonoids, and polyphenolic compounds. These findings will provide critical information for the study of quality standards and medicinal value of RLF and its extracts, justify its usage in traditional medicinal systems, and encourage the use of this plant in disease prevention and treatment. Its phytochemical composition and pharmacological studies need to be explored in future. RESEARCH HIGHLIGHTS: Optical microscope and scanning electron microscope (SEM) were used to observe the morphology, and microstructure of Rosa laxa Retz. flos (RLF). The physicochemical properties, fluorescence and phytochemical composition of four different polar extracts of RLF were analyzed by UV-Vis and FTIR. Determination of total triterpenic acid, total flavonoids, and total polyphenols in four different polar extracts of RLF by UV spectrophotometry. A high-performance liquid chromatography (HPLC)-diode array detector (DAD) method was established and the contents of gallic acid, ellagic acid, astragalin, and tiliroside in RLF were determined simultaneously. TLC confirmed that RLF contains ursolic acid, ß-sitosterol, tiliroside, astragalin, isoquercitrin, kaempferol 3-rutinoside, gallic acid, and ellagic acid. The in vitro antioxidant activity of RLF was studied by DPPH, ABTS, and reducing ability experiments.

9.
Plant Biotechnol J ; 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38923265

RESUMEN

The development of plant virus-based expression systems has expanded rapidly owing to their potential applications in gene functional and disease resistance research, and industrial production of pharmaceutical proteins. However, the low yield of certain proteins, especially high-molecular-mass proteins, restricts the production scale. In this study, we observed that the tobacco mosaic virus (TMV)-mediated expression of a foreign protein was correlated with the amount of the movement protein (MP) and developed a TMV-derived pAT-transMP vector system incorporating trans-complementation expression of MP. The system is capable of efficient expression of exogenous proteins, in particular those with a high molecular mass, and enables simultaneous expression of two target molecules. Furthermore, viral expression of competent CRISPR-Cas9 protein and construction of CRISPR-Cas9-mediated gene-editing system in a single pAT-transMP construct was achieved. The results demonstrated a novel role for TMV-MP in enhancing the accumulation of a foreign protein produced from the viral vector or a binary expression system. Further investigation of the mechanism underlying this role will be beneficial for optimization of plant viral vectors with broad applications.

10.
Chem Sci ; 15(21): 8170-8180, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38817585

RESUMEN

Aqueous electrolytes subjected to angstrom-scale confinement have recently attracted increasing interest because of their distinctive structural and transport properties, as well as their promising applicability in bioinspired nanofluidic iontronics and ion batteries. Here, we performed microsecond-scale molecular dynamics simulations, which provided evidence of nonlinear ionic conductance under an external lateral electric field due to the self-assembly of cations and anions with diverse polyelectrolyte morphologies (e.g., extremely large ion clusters) in aqueous solutions within angstrom-scale slits. Specifically, we found that the cations and anions of Li2SO4 and CaSO4 formed chain-like polyelectrolyte structures, whereas those of Na2SO4 and MgSO4 predominantly formed a monolayer of hydrated salt. Additionally, the cations and anions of K2SO4 assembled into a hexagonal anhydrous ionic crystal. These ion-dependent diverse polyelectrolyte morphologies stemmed from the enhanced Coulomb interactions, weakened hydration and steric constraints within the angstrom-scale slits. More importantly, once the monolayer hydrated salt or ionic crystal structure was formed, the field-induced ion current exhibited an intriguing gating effect at a low field strength. This abnormal ion transport was attributed to the concerted movement of cations and anions within the solid polyelectrolytes, leading to the suppression of ion currents. When the electric field exceeded a critical strength, however, the ion current surged rapidly due to the dissolution of many cations and anions within a few nanoseconds in the aqueous solution.

11.
Heliyon ; 10(9): e30085, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38711659

RESUMEN

Clarifying load transfer mechanism and the influence of the widening of a newly-built railway is the premise for the construction of adjacent project in loess region. This paper uses monitoring datas obtained from three sections in different stages to analyze the distribution laws of load exert on piles and soil between piles, investigates the variation laws of filling height on the earth pressure at different excavation steps and elucidates the influence of the filling height of newly built subgrade on the existing subgrade. In addition, a fitting formula y = a(1-e-bx) + cx is proposed to describe the relationship between the ratio of the additional displacement to the filling height, which is applicable for similar projects.

12.
Gynecol Endocrinol ; 40(1): 2352133, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38749017

RESUMEN

OBJECTIVES: Progestin-primed ovarian stimulation (PPOS) is an efficient controlled ovarian stimulation (COS) method. The study explored the pregnancy outcomes between PPOS and antagonist ovarian stimulation protocol (GnRH-ant) in infertile patients with poor ovarian response (POR). METHODS: This retrospective study included patients with POR who underwent COS at the Reproductive Medical Center of Shanxi Maternal and Child Health Hospital from January 2021 to April 2022. The cycles were grouped as the GnRH-ant group and the PPOS group. The primary outcome was the clinical pregnancy rate; the secondary outcomes included the biochemical pregnancy abortion rate and live birth rate. RESULTS: Frozen embryo transfer was used in all cycles in this study. The cycles were divided into the GnRH-ant (n = 236 cycles) and PPOS (n = 273 cycles) groups. Age, BMI, type of infertility, infertility duration, FSH, LH, PRL, E2, T, P, and the number of cycles in the hospital were similar between the two groups (all p > 0.05). No statistically significant differences were observed in the clinical pregnancy rate (primary outcome, 32.71% vs. 43.90%, p = 0.082), total Gn dose, total Gn days, ART mode (IVF or ICSI), AFC, MII follicles, 2PN embryos, fertility, cycle cancelation rate, biochemical pregnancy rate, abortion rate, or live birth rate between the two groups (all p > 0.05). The PPOS group exhibited a higher rate of high-quality embryos than the GnRH-ant group (50.12% vs. 42.90%, p = 0.045). CONCLUSIONS: The PPOS protocol was comparable to the GnRH-ant protocol regarding induction parameters and cycle cancelation, biochemical pregnancy, clinical pregnancy, and abortion rates but might be associated with a higher proportion of high-quality embryos.


Asunto(s)
Hormona Liberadora de Gonadotropina , Inducción de la Ovulación , Resultado del Embarazo , Índice de Embarazo , Progestinas , Humanos , Femenino , Embarazo , Inducción de la Ovulación/métodos , Estudios Retrospectivos , Adulto , Progestinas/administración & dosificación , Progestinas/uso terapéutico , Resultado del Embarazo/epidemiología , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Infertilidad Femenina/terapia , Transferencia de Embrión/métodos , Antagonistas de Hormonas/uso terapéutico , Antagonistas de Hormonas/administración & dosificación
13.
Cancer Sci ; 115(7): 2444-2460, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38613253

RESUMEN

Peripheral T-cell lymphoma (PTCL) is a highly aggressive type of non-Hodgkin's lymphoma with a poor prognosis. Pyroptosis is a newly discovered procedural cell death mode, which has been implicated to occur in both tumor cells and immune cells. However, the occurrence and effect of pyroptosis on PTCL remain unclear. Here, we found that pyroptosis occurred in interstitial macrophages of PTCL rather than in tumor cells. In clinical specimens, macrophage pyroptosis was associated with a poor prognosis of PTCL. In vitro experiments and gene sequencing results showed that pyroptotic macrophages could upregulate the expression of TLR4 through secreting inflammatory cytokines IL-18. Upregulated TLR4 activated its downstream NF-κB anti-apoptotic signaling pathway, thus leading to malignant proliferation and chemotherapy resistance of tumor cells. Moreover, the expression of factors such as XIAP in the NF-κB anti-apoptotic pathway was downregulated after the knockdown of TLR4, and the malignant promotion effect of pyroptotic macrophages on PTCL cells was also reversed. Our findings revealed the mechanism of pyroptotic macrophages promoting the malignant biological behavior of PTCL and elucidated the key role of TLR4 in this process. In-depth analysis of this mechanism will contribute to understanding the regulatory effect of PTCL by the tumor microenvironment and providing new ideas for the clinical treatment of PTCL.


Asunto(s)
Proliferación Celular , Resistencia a Antineoplásicos , Linfoma de Células T Periférico , Macrófagos , Piroptosis , Transducción de Señal , Receptor Toll-Like 4 , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Humanos , Macrófagos/metabolismo , Macrófagos/inmunología , Resistencia a Antineoplásicos/genética , Piroptosis/efectos de los fármacos , Línea Celular Tumoral , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/genética , Masculino , FN-kappa B/metabolismo , Femenino , Animales , Ratones , Pronóstico , Persona de Mediana Edad , Interleucina-18/metabolismo , Interleucina-18/genética , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica
14.
Top Curr Chem (Cham) ; 382(2): 11, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589726

RESUMEN

Silicone surfactants have garnered significant research attention owing to their superior properties, such as wettability, ductility, and permeability. Small-molecular silicone surfactants with simple molecular structures outperform polymeric silicone surfactants in terms of surface activity, emulsification, wetting, foaming, and other areas. Moreover, silicone surfactants with small molecules exhibit a diverse and rich molecular structure. This review discusses various synthetic routes for the synthesis of different classes of surfactants, including single-chain, "umbrella" structure, double chain, bolaform, Gemini, and stimulus-responsive surfactants. The fundamental surface/interface properties of the synthesized surfactants are also highlighted. Additionally, these surfactants have demonstrated enormous potential in agricultural synergism, drug delivery, mineral flotation, enhanced oil recovery, separation, and extraction, and foam fire-fighting.


Asunto(s)
Siliconas , Tensoactivos , Tensoactivos/química , Propiedades de Superficie , Estructura Molecular
15.
Diabetes Metab Syndr Obes ; 17: 1611-1619, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616993

RESUMEN

Background: Von Hippel-Lindau (VHL) syndrome is characterized by tumorous lesions affecting multiple organs. Pancreatic involvement in VHL syndrome can present as endocrine tumors and pancreatic cysts, which can interfere with both exocrine and endocrine functions of the pancreas. Diabetes is an uncommon complication of VHL syndrome. Purpose: This study aims to summarize the various mechanisms of diabetes in VHL syndrome by reporting two cases and conducting a literature review. Methods: We analyzed the clinical and imaging data of two patients with VHL syndrome and diabetes. Additionally, we reviewed the existing literature to explore the clinical diversities and management strategies for VHL syndrome complicated with diabetes. Results: The first patient presented with liver metastasis of pancreatic neuroendocrine tumor and multiple pheochromocytoma. After surgery, the patient's diabetic control improved, as evidenced by a significant reduction in insulin dosage. This indicates a potential insulin resistance due to elevated metanephrine levels prior to surgery and partial insulin deficiency caused by distal pancreatectomy. The second patient had multiple hemangioblastomas, as well as multiple pancreatic cysts and positive pancreatic islet autoantibodies. Diabetes in this case may be attributed to pancreatic lesions and the coexistence of autoimmune insulitis. A literature review of other patients with VHL combined with diabetes revealed multiple mechanisms, including increased catecholamine levels, pancreatic lesions, surgical removal of pancreatic tissue, endocrine treatment, and possibly the coexistence of autoimmune insulitis. Conclusion: VHL syndrome complicated with diabetes involves diverse mechanisms.

16.
J Chem Phys ; 160(16)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38661200

RESUMEN

In extreme and nanoconfinement conditions, the tetrahedral arrangement of water molecules is challenged, resulting in a rich and new phase behavior unseen in bulk phases. The unique phase behavior of water confined in hydrophobic nanoslits has been previously observed, such as the formation of a variety of two-dimensional (2D) ices below the freezing temperature. The primary identified 2D ice phase, termed square tube ice (STI), represents a unique arrangement of water molecules in 2D ice, which can be viewed as an array of 1D ice nanotubes stacked in the direction parallel to the confinement plane. In this study, we report the molecular dynamics (MD) simulations evidence of a novel 2D ice phase, namely, helical square tube ice (H-STI). H-STI is characterized by the stacking of helical ice nanotubes in the direction parallel to the confinement plane. Its structural specificity is evident in the presence of helical square ice nanotubes, a configuration unseen in both STI and single-walled ice nanotubes. A detailed analysis of the hydrogen bonding strength showed that H-STI is a 2D ice phase diverging from the Bernal-Fowler-Pauling ice rules by forming only two strong hydrogen bonds between adjacent molecules along its helical ice chain. This arrangement of strong hydrogen bonds along ice nanotube and weak bonds between the ice nanotube shows a similarity to quasi-one-dimensional van der Waals materials. Ab initio molecular dynamics simulations (over a 30 ps) were employed to further verify H-STI's stability at 1 GPa and temperature up to 200 K.

17.
Proc Natl Acad Sci U S A ; 121(15): e2315730121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38557188

RESUMEN

Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.

18.
J Hazard Mater ; 471: 134310, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38640677

RESUMEN

Microbial interactions, particularly metabolic cross-feeding, play important roles in removing recalcitrant environmental pollutants; however, the underlying mechanisms involved in this process remain unclear. Thus, this study aimed to elucidate the mechanism by which metabolic cross-feeding occurs during synergistic dibenzofuran degradation between a highly efficient degrader, Rhodococcus sp. strain p52, and a partner incapable of utilizing dibenzofuran. A bottom-up approach combined with pairwise coculturing was used to examine metabolic cross-feeding between strain p52 and Arthrobacter sp. W06 or Achromobacter sp. D10. Pairwise coculture not only promoted bacterial pair growth but also facilitated dibenzofuran degradation. Specifically, strain p52, acting as a donor, released dibenzofuran metabolic intermediates, including salicylic acid and gentisic acid, for utilization and growth, respectively, by the partner strains W06 and D10. Both salicylic acid and gentisic acid exhibited biotoxicity, and their accumulation inhibited dibenzofuran degradation. The transcriptional activity of the genes responsible for the catabolism of dibenzofuran and its metabolic intermediates was coordinately regulated in strain p52 and its cocultivated partners, thus achieving synergistic dibenzofuran degradation. This study provides insights into microbial metabolic cross-feeding during recalcitrant environmental pollutant removal.


Asunto(s)
Biodegradación Ambiental , Rhodococcus , Ácido Salicílico , Rhodococcus/metabolismo , Ácido Salicílico/metabolismo , Dibenzofuranos/metabolismo , Benzofuranos/metabolismo , Gentisatos/metabolismo , Interacciones Microbianas
19.
Medicine (Baltimore) ; 103(14): e37701, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38579043

RESUMEN

RATIONALE: Hysterectomy after microwave ablation (MWA) is more difficult than conventional surgery which increases the probability of postoperative complications due to MWA's collateral thermal damage to nearby intestines. Here we report a case of multiple postoperative complications after hysterectomy following MWA. PATIENT CONCERNS: A 44-year-old female was admitted due to progressive abdominal pain during menstruation for 30 years and no relief 1 year after MWA. Hysterectomy was performed. Intraoperative findings: pelvic inflammatory exudation; the uterus and the left adnexa were extensively and densely adhered to the intestine, bladder, pelvic wall and surrounding tissues; the local tissue of the uterus was brittle and dark yellow. Intestinal obstruction, abdominal infection and urinary fistula occurred after hysterectomy. DIAGNOSES: 1. Adenomyosis. 2. Endometrial polyps. 3. Left chocolate cyst of ovary. 4. Pelvic adhesions. 5. Pelvic inflammation. INTERVENTIONS: The patient underwent intestinal obstruction catheter implantation, ultrasound-guided pelvic fluid mass puncture drainage, right kidney puncture and fistula drainage, right ureteral bladder replantation, and right ureteral stent implantation. OUTCOMES: After 48 days of comprehensive treatment, the patient was cured and discharged. LESSONS: Microwave ablation has a poor therapeutic effect on diffuse adenomyosis, and should avoid excessive ablation during the ablation process.


Asunto(s)
Adenomiosis , Obstrucción Intestinal , Laparoscopía , Femenino , Humanos , Adulto , Adenomiosis/cirugía , Microondas/uso terapéutico , Histerectomía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía
20.
Opt Express ; 32(4): 6258-6265, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439333

RESUMEN

Quasi-two-dimensional perovskites have attracted widespread interest in developing low-cost high-quality small lasers. The nano cavity based on topologically protected valley edge states can be robust against special defects. Here, we report a high-quality two-dimensional perovskite topological photonic crystal laser based on the quantum valley Hall effect. By adjusting the position of the air holes relative to the pillar, radiation leakage in topological edge states is reduced to a large extent, electric field distribution becomes more uniform and the quality factor can be as high as 3.6 × 104. Our findings could provide opportunities for the development of high-power, stable perovskite lasers with topological protection.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...