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1.
Proc Natl Acad Sci U S A ; 121(6): e2318341121, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38289957

RESUMEN

As a prototypical photocatalyst, TiO[Formula: see text] has been extensively studied. An interesting yet puzzling experimental fact was that P25-a mixture of anatase and rutile TiO[Formula: see text]-outperforms the individual phases; the origin of this mysterious fact, however, remains elusive. Employing rigorous first-principles calculations, here we uncover a metastable intermediate structure (MIS), which is formed due to confinement at the anatase/rutile interface. The MIS has a high conduction-band minimum level and thus substantially enhances the overpotential of the hydrogen evolution reaction. Also, the corresponding band alignment at the interface leads to efficient separation of electrons and holes. The interfacial confinement additionally creates a wide distribution of the band gap in the vicinity of the interface, which in turn improves optical absorption. These factors all contribute to the enhanced photocatalytic efficiency in P25. Our insights provide a rationale to the puzzling superior photocatalytic performance of P25 and enable a strategy to achieve highly efficient photocatalysis via interface engineering.

2.
J Am Chem Soc ; 146(18): 12864-12876, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38670931

RESUMEN

Deep-ultraviolet (DUV) light sources are technologically highly important, but DUV light-emitting materials are extremely rare; AlN and its alloys are the only materials known so far, significantly limiting the chemical and structural spaces for materials design. Here, we perform a high-throughput computational search for DUV light emitters based on a set of carefully designed screening criteria relating to the sophisticated electronic structure. In this way, we successfully identify 5 promising material candidates that exhibit comparable or higher radiative recombination coefficients than AlN, including BeGeN2, Mg3NF3, KCaBr3, KHS, and RbHS. Further, we unveil the unique features in the atomic and electronic structures of DUV light emitters and elucidate the fundamental genetic reasons why DUV light emitters are extremely rare. Our study not only guides the design and synthesis of efficient DUV light emitters but also establishes the genetic nature of ultrawide-band-gap semiconductors in general.

3.
Br J Haematol ; 205(4): 1477-1488, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39099079

RESUMEN

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.


Asunto(s)
Encefalitis Viral , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Masculino , Femenino , Encefalitis Viral/etiología , Encefalitis Viral/diagnóstico , Adulto , Pronóstico , Estudios Retrospectivos , Persona de Mediana Edad , Adolescente , Factores de Riesgo , Trombocitopenia/etiología , Trasplante Homólogo/efectos adversos , Niño , Imagen por Resonancia Magnética , Adulto Joven
4.
Anal Chem ; 96(17): 6550-6557, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38642045

RESUMEN

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

5.
Radiology ; 310(3): e230397, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38441089

RESUMEN

Background Translocator protein (TSPO) PET has been used to visualize microglial activation in neuroinflammation and is a potential imaging tool for detecting autoimmune encephalitis (AIE). Purpose To compare the detection rate between TSPO radioligand fluorine 18 (18F) DPA-714 PET and conventional MRI and assess the relationship between 18F-DPA-714 uptake and clinical features in participants with AIE. Materials and Methods Healthy volunteers and patients with AIE were enrolled in this prospective study between December 2021 and April 2023. All participants underwent hybrid brain 18F-DPA-714 PET/MRI and antibody testing. Modified Rankin scale scoring and AIE-related symptoms were assessed in participants with AIE. Positive findings were defined as intensity of 18F-DPA-714 uptake above a threshold of the mean standardized uptake value ratio (SUVR) plus 2 SD inside the corresponding brain regions of healthy controls. The McNemar test was used to compare the positive detection rate between the two imaging modalities; the independent samples t test was used to compare continuous variables; and correlation with Bonferroni correction was used to assess the relationship between 18F-DPA-714 uptake and clinical features. Results A total of 25 participants with AIE (mean age, 39.24 years ± 19.03 [SD]) and 10 healthy controls (mean age, 28.70 years ± 5.14) were included. The positive detection rate of AIE was 72% (18 of 25) using 18F-DPA-714 PET compared to 44% (11 of 25) using conventional MRI, but the difference was not statistically significant (P = .065). Participants experiencing seizures exhibited significantly higher mean SUVR in the entire cortical region than those without seizures (1.23 ± 0.21 vs 1.15 ± 0.18; P = .003). Of the 13 participants with AIE who underwent follow-up PET/MRI, 11 (85%) demonstrated reduced uptake of 18F-DPA-714 accompanied by relief of symptoms after immunosuppressive treatment. Conclusion 18F-DPA-714 PET has potential value in supplementing MRI for AIE detection. Clinical trial registration no. NCT05293405 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Zaharchuk in this issue.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Encefalitis , Enfermedad de Hashimoto , Microglía , Pirazoles , Pirimidinas , Humanos , Adulto , Estudios Prospectivos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Convulsiones , Receptores de GABA
6.
J Med Virol ; 96(1): e29396, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38235848

RESUMEN

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.


Asunto(s)
COVID-19 , Coronavirus del Síndrome Respiratorio de Oriente Medio , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , COVID-19/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Factores de Empalme de ARN
7.
Blood ; 139(3): 333-342, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-34665865

RESUMEN

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.


Asunto(s)
Antineoplásicos/uso terapéutico , Factores Inmunológicos/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Rituximab/uso terapéutico , Tretinoina/uso terapéutico , Corticoesteroides/uso terapéutico , Adulto , Antineoplásicos/administración & dosificación , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia , Rituximab/administración & dosificación , Prevención Secundaria , Tretinoina/administración & dosificación
8.
Artículo en Inglés | MEDLINE | ID: mdl-39060373

RESUMEN

PURPOSE: Generating polar map (PM) from [68Ga]Ga-DOTA-FAPI-04 PET images is challenging and inaccurate using existing automatic methods that rely on the myocardial anatomical integrity in PET images. This study aims to enhance the accuracy of PM generated from [68Ga]Ga-DOTA-FAPI-04 PET images and explore the potential value of PM in detecting reactive fibrosis after myocardial infarction and assessing its relationship with cardiac function. METHODS: We proposed a deep-learning-based method that fuses multi-modality images to compensate for the cardiac structural information lost in [68Ga]Ga-DOTA-FAPI-04 PET images and accurately generated PMs. We collected 133 pairs of [68Ga]Ga-DOTA-FAPI-04 PET/MR images from 87 ST-segment elevated myocardial infarction patients for training and evaluation purposes. Twenty-six patients were selected for longitudinal analysis, further examining the clinical value of PM-related imaging parameters. RESULTS: The quantitative comparison demonstrated that our method was comparable with the manual method and surpassed the commercially available software-PMOD in terms of accuracy in generating PMs for [68Ga]Ga-DOTA-FAPI-04 PET images. Clinical analysis revealed the effectiveness of [68Ga]Ga-DOTA-FAPI-04 PET PM in detecting reactive myocardial fibrosis. Significant correlations were demonstrated between the difference of baseline PM FAPI% and PM LGE%, and the change in cardiac function parameters (all p < 0.001), including LVESV% (r = 0.697), LVEDV% (r = 0.621) and LVEF% (r = -0.607). CONCLUSION: The [68Ga]Ga-DOTA-FAPI-04 PET PMs generated by our method are comparable to manually generated and sufficient for clinical use. The PMs generated by our method have potential value in detecting reactive fibrosis after myocardial infarction and were associated with cardiac function, suggesting the possibility of enhancing clinical diagnostic practices. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04723953). Registered 26 January 2021.

9.
Am J Hematol ; 99(10): 1951-1958, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38980207

RESUMEN

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.


Asunto(s)
Azetidinas , Resistencia a Medicamentos , Purinas , Púrpura Trombocitopénica Idiopática , Pirazoles , Sulfonamidas , Humanos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Sulfonamidas/administración & dosificación , Azetidinas/uso terapéutico , Azetidinas/administración & dosificación , Azetidinas/efectos adversos , Purinas/uso terapéutico , Purinas/efectos adversos , Purinas/administración & dosificación , Masculino , Proyectos Piloto , Femenino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto , Anciano , Recurrencia , Resultado del Tratamiento , Recuento de Plaquetas
10.
J Nanobiotechnology ; 22(1): 97, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454419

RESUMEN

Immune checkpoint blockers (ICBs) have been applied for cancer therapy and achieved great success in the field of cancer immunotherapy. Nevertheless, the broad application of ICBs is limited by the low response rate. To address this issue, increasing studies have found that the induction of immunogenic cell death (ICD) in tumor cells is becoming an emerging therapeutic strategy in cancer treatment, not only straightly killing tumor cells but also enhancing dying cells immunogenicity and activating antitumor immunity. ICD is a generic term representing different cell death modes containing ferroptosis, pyroptosis, autophagy and apoptosis. Traditional chemotherapeutic agents usually inhibit tumor growth based on the apoptotic ICD, but most tumor cells are resistant to the apoptosis. Thus, the induction of non-apoptotic ICD is considered to be a more efficient approach for cancer therapy. In addition, due to the ineffective localization of ICD inducers, various types of nanomaterials have been being developed to achieve targeted delivery of therapeutic agents and improved immunotherapeutic efficiency. In this review, we briefly outline molecular mechanisms of ferroptosis, pyroptosis and autophagy, as well as their reciprocal interactions with antitumor immunity, and then summarize the current progress of ICD-induced nanoparticles based on different strategies and illustrate their applications in the cancer therapy.


Asunto(s)
Ferroptosis , Nanopartículas , Neoplasias , Humanos , Piroptosis , Inmunoterapia , Autofagia , Inhibidores de Puntos de Control Inmunológico , Neoplasias/terapia
11.
BMC Health Serv Res ; 24(1): 1167, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39363315

RESUMEN

BACKGROUND AND AIM: China has used traditional Chinese medicine (TCM) to treat diseases for more than 2000 years. Traditionally, TCMs in medicine cabinets are arranged alphabetically or on the basis of experience, but this arrangement greatly affects dispensing efficiency. However, owing to the unique properties and qualities of TCM, very few automatic approaches or systems have specifically addressed TCM dispensing problems. Therefore, it is necessary to establish a method of optimizing the traditional Chinese medicine placement scheme (TCMPS) via computer algorithms to improve the work efficiency of pharmacists. METHODS: A prescription dataset from a hospital in 2022 was obtained, and the association rule algorithm (ARA) was used to calculate the frequency of use for each type of TCM and the associations between different types of TCMs. On the basis of these association and frequency data, the optimal TCMPS was calculated using the simulated annealing algorithm (SAA) and then verified using the prescription dataset from 2023. RESULTS: A total of 10,601 prescriptions were collected in 2022, involving 360 different TCMs, and each prescription contained an average of 9.485 TCMs, with Danggui (3628) being the most frequently used. When the threshold of support was set to 0.05 and the confidence was set to 0.8, 78 couplet medicines used in orthopedics clinics were found through ARA. When the threshold value of support was set to 0, the confidence was set to 0, and the rule length was 2, a total of 129,240 rules were obtained, indicating support between all pairwise TCMs. The TCMPS, calculated using SAA, had a correlation sum of 14.183 and a distance sum of 3.292. The TCMPS was verified using a prescription dataset from 2023 and theoretically improved the dispensing efficiency of pharmacists by approximately 50%. CONCLUSIONS: In this study, the ARA and SAA were successfully applied to pharmacies for the first time, and the optimal TCMPS was calculated. This approach not only significantly improves the dispensing efficiency of pharmacists and reduces patient waiting time but also enhances the quality of medical services and patient satisfaction, and provides a valuable reference for the development of smart medicine.


Asunto(s)
Algoritmos , Medicina Tradicional China , Medicina Tradicional China/métodos , Humanos , China , Servicio de Farmacia en Hospital , Medicamentos Herbarios Chinos/normas , Medicamentos Herbarios Chinos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Prescripciones de Medicamentos/normas
12.
J Xray Sci Technol ; 32(4): 993-1009, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728198

RESUMEN

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Linfoma/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Adulto , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Anciano
13.
Haematologica ; 108(9): 2316-2330, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36475518

RESUMEN

Mono-allelic germline disruptions of the transcription factor GATA2 result in a propensity for developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), affecting more than 85% of carriers. How a partial loss of GATA2 functionality enables leukemic transformation years later is unclear. This question has remained unsolved mainly due to the lack of informative models, as Gata2 heterozygote mice do not develop hematologic malignancies. Here we show that two different germline Gata2 mutations (TgErg/Gata2het and TgErg/Gata2L359V) accelerate AML in mice expressing the human hematopoietic stem cell regulator ERG. Analysis of Erg/Gata2het fetal liver and bone marrow-derived hematopoietic cells revealed a distinct pre-leukemic phenotype. This was characterized by enhanced transition from stem to progenitor state, increased proliferation, and a striking mitochondrial phenotype, consisting of highly expressed oxidative-phosphorylation-related gene sets, elevated oxygen consumption rates, and notably, markedly distorted mitochondrial morphology. Importantly, the same mitochondrial gene-expression signature was observed in human AML harboring GATA2 aberrations. Similar to the observations in mice, non-leukemic bone marrows from children with germline GATA2 mutation demonstrated marked mitochondrial abnormalities. Thus, we observed the tumor suppressive effects of GATA2 in two germline Gata2 genetic mouse models. As oncogenic mutations often accumulate with age, GATA2 deficiency-mediated priming of hematopoietic cells for oncogenic transformation may explain the earlier occurrence of MDS/AML in patients with GATA2 germline mutation. The mitochondrial phenotype is a potential therapeutic opportunity for the prevention of leukemic transformation in these patients.


Asunto(s)
Deficiencia GATA2 , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Niño , Humanos , Ratones , Animales , Deficiencia GATA2/genética , Síndromes Mielodisplásicos/patología , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Médula Ósea/patología , Células Madre Hematopoyéticas/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Factor de Transcripción GATA2/genética , Factor de Transcripción GATA2/metabolismo
14.
Inorg Chem ; 62(37): 14998-15005, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37655478

RESUMEN

Although ionic liquids (ILs) are of prime interest for the synthesis of various nanomaterials, they are scarcely utilized for the polyhydrido copper(I) [Cu(I)H] clusters. Herein, two air-stable Cu(I)H clusters, [Cu8H6(dppy)6](NTf2)2 (Cu8H6) and {Cu12H9(dppy)6[N(CN)2]3} (Cu12H9), are synthesized in high yields for the first time from the ILs-driven conversion of an unprecedented cluster [Cu7H5(dppy)6](ClO4)2 (Cu7H5) by a facile three-layers diffusion crystal (TLDC) method, strategically introducing IL-NTf2 and IL-N(CN)2 as two types of unusual interfacial crystallized templates, respectively. Their structures are fully characterized by various spectroscopic methods and X-ray crystallography, which shows that the anion of IL plays an important role as an anion template and an anion ligand in controlling the structural conversion of Cu(I)H clusters. Their photophysical properties are also investigated, and it is found that all reported clusters exhibit red luminescence with λem ranging from 600 to 690 nm.

15.
Bioorg Chem ; 133: 106382, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36716580

RESUMEN

Acute pancreatitis (AP) is a frequent abdominal inflammatory disease. Despite the high morbidity and mortality, the management of AP remains unsatisfactory. Disulfiram (DSF) is an FDA-proved drug with potential therapeutic effects on inflammatory diseases. In this study, we aim to investigate the effect of DSF on pancreatic acinar cell necrosis, and to explore the underlying mechanisms. Cell necrosis was induced by sodium taurocholate or caerulein, AP mice model was induced by nine hourly injections of caerulein. Network pharmacology, molecular docking, and molecular dynamics simulation were used to explore the potential targets of DSF in protecting against cell necrosis. The results indicated that DSF significantly inhibited acinar cell necrosis as evidenced by a decreased ratio of necrotic cells in the pancreas. Network pharmacology, molecular docking, and molecular dynamics simulation identified RIPK1 as a potent target of DSF in protecting against acinar cell necrosis. qRT-PCR analysis revealed that DSF decreased the mRNA levels of RIPK1 in freshly isolated pancreatic acinar cells and the pancreas of AP mice. Western blot showed that DSF treatment decreased the expressions of RIPK1 and MLKL proteins. Moreover, DSF inhibited NF-κB activation in acini. It also decreased the protein expression of TLR4 and the formation of neutrophils extracellular traps (NETs) induced by damage-associated molecular patterns released by necrotic acinar cells. Collectively, DSF could ameliorate the severity of mouse acute pancreatitis by inhibiting RIPK-dependent acinar cell necrosis and the following formation of NETs.


Asunto(s)
Pancreatitis , Ratones , Animales , Pancreatitis/tratamiento farmacológico , Pancreatitis/inducido químicamente , Células Acinares , Disulfiram/efectos adversos , Ceruletida/efectos adversos , Enfermedad Aguda , Simulación del Acoplamiento Molecular , Necrosis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/farmacología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/uso terapéutico
16.
Ecotoxicol Environ Saf ; 263: 115213, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37421895

RESUMEN

Aflatoxin is the most common type of mycotoxins in contaminated corn, peanuts and rice, which affects the livestock and ultimately endangers human health. Aflatoxin is reported to have carcinogenicity, mutation, growth retardation, immunosuppression and reproductive toxicity. In present study we reported the causes for the declined porcine oocyte quality under aflatoxin exposure. We set up an in vitro exposure model and showed that aflatoxin B1 disturbed cumulus cell expansion and oocyte polar body extrusion. We found that aflatoxin B1 exposure disrupted ER distribution and elevated the expression of GRP78, indicating the occurrence of ER stress, and the increased calcium storage also confirmed this. Besides, the structure of cis-Golgi apparatus, another intracellular membrane system was also affected, showing with decreased GM130 expression. The oocytes under aflatoxin B1 exposure showed aberrant lysosome accumulation and higher LAMP2 expression, a marker for lysosome membrane protection, and this might be due to the aberrant mitochondria function with low ATP production and the increase of apoptosis, since we found that BAX expression increased, and ribosomal protein which is also an apoptosis-related factor RPS3 decreased. Taken together, our study revealed that aflatoxin B1 impairs intracellular membrane system ER, Golgi apparatus, lysosome and mitochondria function to affect porcine oocyte maturation quality.


Asunto(s)
Aflatoxina B1 , Oocitos , Humanos , Animales , Porcinos , Aflatoxina B1/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Oocitos/metabolismo , Apoptosis , Membranas Intracelulares , Adenosina Trifosfato/metabolismo
17.
BMC Surg ; 23(1): 158, 2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37312138

RESUMEN

PURPOSE: This investigation aimed to compare the medical efficacy of the knotted and knotless suture-bridge procedures in rotator cuff repair. METHODS: The Pubmed, Embase, and Cochrane Library datasets were searched for all available publications comparing the medical results of arthroscopic rotator cuff repairs utilizing knotted or knotless suture-bridge procedures. Two researchers utilized Newcastle-Ottawa Scale and Cochrane risk-of-bias tool to evaluate the included studies. Employing Revman 5.3 software, meta-analysis was conducted following the PRISMA reporting guideline. RESULTS: Eleven investigations with 1083 patients were considered suitable for the final meta-analysis. 522 individuals were assigned to the knotted group, whereas 561 were assigned to the knotless group. No statistical difference was found between the knotted and knotless groups, regarding VAS score (WMD, 0.17; 95% CI, - 0.10 to 0.44; P = 0.21); Constant score (WMD, -1.50; 95% CI, - 3.52 to 0.52; P = 0.14); American Shoulder and Elbow Surgeons Shoulder (WMD, -2.02; 95% CI, - 4.53 to 0.49; P = 0.11); University of California Los Angeles score (WMD, -0.13; 95% CI, - 0.89 to 0.63; P = 0.73); ROM of flexion (WMD, 1.57; 95% CI, - 2.11 to 5.60; P = 0.37), abduction (WMD, 1.08; 95% CI, - 4.53 to 6.70; P = 0.71) and external rotation (WMD, 1.90; 95% CI, - 1.36 to 5.16; P = 0.25); re-tear rate (OR, 0.74; 95% CI, 0.50 to 1.08; P = 0.12), and medical complications (OR, 0.90; 95% CI, 0.37 to 2.20; P = 0.82). CONCLUSION: For arthroscopic rotator cuff repairs, there were no statistical differences in medical results among knotted and knotless suture-bridge procedures. Overall, both techniques showed excellent clinical outcomes and could be safely utilized to treat rotator cuff injuries.


Asunto(s)
Articulación del Codo , Laceraciones , Humanos , Manguito de los Rotadores/cirugía , Procedimientos Neuroquirúrgicos , Suturas
18.
Chin J Traumatol ; 26(6): 317-322, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37926628

RESUMEN

PURPOSE: To investigate the clinical effects of arthroscopically artificial ligament reconstruction with tensional remnant-repair in patients who are obese, and/or with demand for highly intensive sports, and/or with poor-quality ligament remnants. METHODS: A retrospective case series study was performed on patients treated by arthroscopically anterior talofibular ligament (ATFL) reconstruction with tensional remnant repair technique from January 2019 to August 2021. General data, including demographics, surgical time, and postoperative adverse events, were recorded. The American Orthopaedic Foot and Ankle Society score (AOFAS), foot and ankle ability measure (FAAM), visual analog scale (VAS), and anterior talar translation were measured preoperatively and at 6 weeks, 3 months, and 2 years postoperatively. Ultrasonography examination was performed preoperatively and 2 years postoperatively to evaluate the ATFL. Data were analyzed using SPSS 19.0. F test was used to analyze the pre- and postoperative VAS, FAAM, and AOFAS scores. The significance was set at p < 0.05. RESULTS: There were 20 males and 10 females among the patients with a mean age of (30.71 ± 5.81) years. The average surgical time was (40.21 ± 8.59) min. No adverse events were observed after surgery. At 2 years postoperatively, the anterior talar translation test showed grade 0 laxity in all patients. VAS score significantly decreased from preoperatively to 6 weeks, 3 months, and 2 years postoperatively (p < 0.001). Improvement of FAAM score and the AOFAS score from preoperatively to 6 weeks, 3 months, and 2 years postoperatively was statistically significant (p < 0.001). At 3 months postoperatively, most patients (23/30) could return to their pre-injured activities of daily living status. At 2 years postoperatively, all patients were able to return to their pre-injured activities of daily living status, and almost every patient (18/19) who expected highly intensive sports returned to sports with only 1 obese patient failing to achieve the goal. The ultrasonography examination at 2 years postoperatively showed that there was a linear band structure of soft tissue on the tension-rich fiber tape image from the fibular to the talar attachment sits of ATFL. CONCLUSION: The novel arthroscopically artificial ligament reconstruction with tensional remnant-repair technique for ATFL achieved satisfactory clinical outcomes in the short and medium term after operation, and allowed early return to pre-injured activities, which could be a reliable option for patients with chronic lateral ankle instability.


Asunto(s)
Traumatismos del Tobillo , Inestabilidad de la Articulación , Ligamentos Laterales del Tobillo , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Articulación del Tobillo/cirugía , Estudios Retrospectivos , Actividades Cotidianas , Traumatismos del Tobillo/cirugía , Ligamentos Laterales del Tobillo/cirugía , Inestabilidad de la Articulación/cirugía , Ligamentos , Obesidad , Artroscopía/métodos
19.
Zhongguo Zhong Yao Za Zhi ; 48(2): 525-533, 2023 Jan.
Artículo en Zh | MEDLINE | ID: mdl-36725242

RESUMEN

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , ARN Ribosómico 16S , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ocludina/metabolismo , Ocludina/farmacología , Claudina-1/metabolismo , Mucosa Intestinal , Hígado , Triglicéridos/metabolismo , Dieta Alta en Grasa , Homeostasis , Ratones Endogámicos C57BL
20.
Angew Chem Int Ed Engl ; 62(13): e202218229, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36714922

RESUMEN

The application of solid polymer electrolytes (SPEs) in all-solid-state(ASS) batteries is hindered by lower Li+ -conductivity and narrower electrochemical window. Here, three families of ester-based F-modified SPEs of poly-carbonate (PCE), poly-oxalate (POE) and poly-malonate (PME) were investigated. The Li+ -conductivity of these SPEs prepared from pentanediol are all higher than the counterparts made of butanediol, owing to the enhanced asymmetry and flexibility. Because of stronger chelating coordination with Li+ , the Li+ -conductivity of PME and POE is around 10 and 5 times of PCE. The trifluoroacetyl-units are observed more effective than -O-CH2 -CF2 -CF2 -CH2 -O- during the in situ passivation of Li-metal. Using trifluoroacetyl terminated POE and PCE as SPE, the interfaces with Li-metal and high-voltage-cathode are stabilized simultaneously, endowing stable cycling of ASS Li/LiNi0.6 Co0.2 Mn0.2 O2 (NCM622) cells. Owing to an enol isomerization of malonate, the cycling stability of Li/PME/NCM622 is deteriorated, which is recovered with the introduce of dimethyl-group in malonate and the suppression of enol isomerization. The coordinating capability with Li+ , molecular asymmetry and existing modes of elemental F, are all critical for the molecular design of SPEs.

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