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1.
Inorg Chem ; 63(15): 6714-6722, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38557020

RESUMEN

Converting CO2 into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO2 reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO2@Bi2WO6 heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO2@Bi2WO6 photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi(3-x)+ sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 µmol h-1 g-1, which is 15 and 4.7 times higher than that of pure Bi2WO6 and that of physically mixed TiO2/Bi2WO6, respectively. An in situ study shows that the pathway for the transformation of CO2 into CO over our TiO2@Bi2WO6 proceeds via two important intermediates, including COO- and COOH-. Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO2 conversion.

2.
Opt Express ; 32(6): 8877-8886, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571134

RESUMEN

The limited pattern area of periodic nanostructures limits the development of practical devices. This study introduces an X-ray interference lithography (XIL) stitching technique to fabricate a large-area (1.5 cm × 1.5 cm) two-dimensional photonic crystal (PhC) on the YAG: Ce scintillator, which functions as an encoder in a high numerical aperture optical encoding imaging system to effectively capture high-frequency information. An X-ray imaging experiment revealed a substantial 7.64 dB improvement in the signal-to-noise ratio (SNR) across a large field of view (2.6 mm × 2.6 mm) and achieved comparable or superior image quality with half the exposure dose. These findings have significant implications for advancing practical applications of X-ray imaging.

3.
J Immunol ; 212(10): 1589-1601, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38558134

RESUMEN

Tumor-targeting Abs can be used to initiate an antitumor immune program, which appears essential to achieve a long-term durable clinical response to cancer. We previously identified an anti-complement factor H (CFH) autoantibody associated with patients with early-stage non-small cell lung cancer. We cloned from their peripheral B cells an mAb, GT103, that specifically recognizes CFH on tumor cells. Although the underlying mechanisms are not well defined, GT103 targets a conformationally distinct CFH epitope that is created when CFH is associated with tumor cells, kills tumor cells in vitro, and has potent antitumor activity in vivo. In the effort to better understand how an Ab targeting a tumor epitope can promote an effective antitumor immune response, we used the syngeneic CMT167 lung tumor C57BL/6 mouse model, and we found that murinized GT103 (mGT103) activates complement and enhances antitumor immunity through multiple pathways. It creates a favorable tumor microenvironment by decreasing immunosuppressive regulatory T cells and myeloid-derived suppressor cells, enhances Ag-specific effector T cells, and has an additive antitumor effect with anti-PD-L1 mAb. Furthermore, the immune landscape of tumors from early-stage patients expressing the anti-CFH autoantibody is associated with an immunologically active tumor microenvironment. More broadly, our results using an mAb cloned from autoantibody-expressing B cells provides novel, to our knowledge, mechanistic insights into how a tumor-specific, complement-activating Ab can generate an immune program to kill tumor cells and inhibit tumor growth.


Asunto(s)
Activación de Complemento , Ratones Endogámicos C57BL , Animales , Ratones , Humanos , Activación de Complemento/inmunología , Línea Celular Tumoral , Factor H de Complemento/inmunología , Microambiente Tumoral/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/uso terapéutico , Autoanticuerpos/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Femenino , Linfocitos T Reguladores/inmunología
4.
Cell Signal ; 117: 111094, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38341123

RESUMEN

Hypoxia-inducible transcription factors (HIFs) are key transcription factors for cellular response to low oxygen levels. However, the specific mediators responsible for activating downstream transcription are not well characterized. We previously identified Protein Arginine methyltransferase 2 (PRMT2), a highly expressed methyltransferase in glioblastoma multiforme, as a transcription co-activator. And we established a connection between PRMT2-mediated histone H3R8 asymmetric methylation (H3R8me2a) and transcription activation. Here we find that PRMT2 is activated by HIF1α under hypoxic conditions. And we demonstrate that PRMT2 and its H3R8me2a activity are required for the transcription activation of a significant subset of hypoxia-induced genes. Consequently, the inactivation of PRMT2 suppresses hypoxia-induced glioblastoma cell migration, attenuates tumor progression, and enhances chemotherapeutic sensitivity in mouse xenograft models. In addition, our analysis of clinical glioma specimens reveals a correlation between PRMT2 protein levels, HIF1α abundance, and an unfavorable prognosis. Our study establishes HIF1α-induced PRMT2 as a critical modulator in the activation of hypoxia-related transcriptional programs, ultimately driving malignant progression.


Asunto(s)
Glioblastoma , Humanos , Ratones , Animales , Glioblastoma/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Factores de Transcripción/metabolismo , Metilación , Activación Transcripcional , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo
5.
Front Cell Dev Biol ; 12: 1302490, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38389705

RESUMEN

The elimination of cancer cells critically depends on the immune system. However, cancers have evolved a variety of defense mechanisms to evade immune monitoring, leading to tumor progression. Complement factor H (CFH), predominately known for its function in inhibiting the alternative pathway of the complement system, has recently been identified as an important innate immunological checkpoint in cancer. CFH-mediated immunosuppression enhances tumor cells' ability to avoid immune recognition and produce an immunosuppressive tumor microenvironment. This review explores the molecular underpinnings, interactions with immune cells, clinical consequences, and therapeutic possibilities of CFH as an innate immune checkpoint in cancer control. The difficulties and opportunities of using CFH as a target in cancer immunotherapy are also explored.

6.
Dalton Trans ; 53(6): 2526-2533, 2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38226637

RESUMEN

Excessive emission of CO2 into the atmosphere has severely impacted the global ecological environment. Converting CO2 into valuable chemicals and fuels is of great significance for sustainable development. However, low activity and undesirable selectivity often result from the inherent inertness of CO2. Herein, K- or/and Zn-modified Fe-based catalysts were prepared by an incipient-wetness impregnation method for CO2 hydrogenation via a cascade reaction. The results indicate that K species exist as K2O while Zn species exist as ZnFe2O4. In the CO2 hydrogenation pathway, K2O facilitates the adsorption of CO2 and restrains the adsorption of H2, accelerating the transformation of CO2 into C2-C4 olefins rather than paraffins while Zn species promote the dispersion of Fe species, leading to improved activity. Synergistically, a K- and Zn-modified Fe-based catalyst (2Zn-10K-Fe/Al) shows excellent catalytic CO2 hydrogenation activity, achieving a CO2 conversion of 77% which is 1.8 times that (42%) of the unmodified Fe-based catalyst (Fe/Al). Our catalyst also shows a significantly promoted selectivity to C2-C4 olefins of 17% in comparison with the Fe/Al catalyst (0%). It is envisioned that such a binary effect of elements might contribute to the low-cost and industrial production of Fe-based catalysts for selective CO2 conversion.

7.
Breast Cancer Res Treat ; 204(1): 89-105, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38066250

RESUMEN

PURPOSE: To investigate potential differences in pathological complete response (pCR) rates and overall survival (OS) between HER2-low and HER2-zero patients with early-stage hormone receptor (HR)-positive and triple-negative breast cancer (TNBC), in the neoadjuvant chemotherapy setting. METHODS: We identified early-stage invasive HER2-negative BC patients who received neoadjuvant chemotherapy diagnosed between 2010 and 2018 in the National Cancer Database. HER2-low was defined by immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization, and HER2-zero by IHC0. All the methods were applied separately in the HR-positive and TNBC cohorts. Logistic regression was used to estimate the association of HER2 status with pCR (i.e. ypT0/Tis and ypN0). Kaplan-Meier method and Cox proportional hazards model were applied to estimate the association of HER2 status with OS. Inverse probability weighting and/or multivariable regression were applied to all analyses. RESULTS: For HR-positive patients, 70.9% (n = 17,934) were HER2-low, whereas 51.1% (n = 10,238) of TNBC patients were HER2-low. For both HR-positive and TNBC cohorts, HER2-low status was significantly associated with lower pCR rates [HR-positive: 5.0% vs. 6.7%; weighted odds ratio (OR) = 0.81 (95% CI: 0.72-0.91), p < 0.001; TNBC: 21.6% vs. 24.4%; weighted OR = 0.91 (95% CI: 0.85-0.98), p = 0.007] and improved OS [HR-positive: weighted hazard ratio = 0.85 (95% CI: 0.79-0.91), p < 0.001; TNBC: weighted hazard ratio = 0.91 (95% CI: 0.86-0.96), p < 0.001]. HER2-low status was associated with favorable OS among patients not achieving pCR [HR-positive: adjusted hazard ratio = 0.83 (95% CI: 0.77-0.89), p < 0.001; TNBC: adjusted hazard ratio = 0.88 (95% CI 0.83-0.94), p < 0.001], while no significant difference in OS was observed in patients who achieved pCR [HR-positive: adjusted hazard ratio = 1.00 (95% CI: 0.61-1.63), p > 0.99; TNBC: adjusted hazard ratio = 1.11 (95% CI: 0.85-1.45), p = 0.44]. CONCLUSION: In both early-stage HR-positive and TNBC patients, HER2-low status was associated with lower pCR rates. HER2-zero status might be considered an adverse prognostic factor for OS in patients not achieving pCR.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Terapia Neoadyuvante/efectos adversos , Modelos de Riesgos Proporcionales , Receptor ErbB-2/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pronóstico
8.
Int J Gynaecol Obstet ; 165(1): 194-202, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38009672

RESUMEN

OBJECTIVE: Endometrioid ovarian cancer (EnOC) accounts for approximately 10%-15% of epithelial ovarian cancer cases. There are no effective tools for predicting the prognosis of EnOC in clinical work. The aim of this study was to construct and validate a nomogram to predict overall survival and cancer-specific survival (CSS) in patients with EnOC. METHODS: Data regarding patients diagnosed with primary EnOC between 2004 and 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. LASSO Cox regression and Cox regression analyses were performed to screen for prognostic factors, which were used to construct nomograms. In addition, we performed subgroup analyses of the prognostic value of chemotherapy and lymph node surgery. RESULTS: In total, 3957 patients with primary EnOC were included in the analysis: 2770 in a training cohort and 1187 in a validation cohort. Age, stage, grade, lymph node surgery, and race were significantly and independently correlated with overall survival and CSS. Nomograms were constructed to predict 3- and 5-year overall survival and CSS. Nomograms have good predictive ability and clinical practicability. Subgroup analysis showed that lymph node surgery improved the prognosis of patients with EnOC (P < 0.05) except for patients with grade III-IV and Stage I disease (overall survival P = 0.272, CSS P = 0.624). Chemotherapy did not improve survival time in most patients (P > 0.05) except for patients with grade I-II and Stage II-IV disease (overall survival P = 0.008, CSS P = 0.046). CONCLUSION: We constructed predictive nomograms and a risk classification system to evaluate overall survival and CSS in EnOC patients. For most patients with EnOC, chemotherapy did not improve the prognosis. In contrast to chemotherapy, lymph node surgery improved prognosis in most patients with EnOC.


Asunto(s)
Carcinoma Endometrioide , Neoplasias Ováricas , Femenino , Humanos , Nomogramas , Carcinoma Epitelial de Ovario/terapia , Estudios Retrospectivos , Carcinoma Endometrioide/terapia , Neoplasias Ováricas/terapia , Programa de VERF , Pronóstico , Estadificación de Neoplasias
9.
Huan Jing Ke Xue ; 44(12): 6433-6440, 2023 Dec 08.
Artículo en Chino | MEDLINE | ID: mdl-38098372

RESUMEN

Meteorological conditions play a key role in the occurrence and evolution of atmospheric complex pollution. Considering the different pollution formation mechanisms of PM2.5 and O3, statistical calculation and in-depth learning methods were used to construct the PM2.5 and O3 meteorological condition indexes based on long-term pollution meteorological observation data. A research method was developed to study the meteorological characteristics and impact contribution of atmospheric complex pollution by using the meteorological condition index, and quantitative analysis of the distribution and variation of pollution excluding the influence of regional meteorological differences was also conducted. The results showed that in the summer of 2021, the pollution meteorological conditions in the key regions in central and eastern China were generally worse in the north and better in the south(index:"2+26" cities>the border area of Jiangsu, Anhui, Shandong, and Henan>the Yangtze River Delta) and the worst in June and the best in July. The "double high" pollution began to appear when the PM2.5 meteorological condition index>30 and O3 meteorological condition index>100; meanwhile, the unfavorable meteorological conditions for O3 also promoted the increase in PM2.5 concentration, resulting in the frequency of "double high" increases with the increase in O3 meteorological condition index. Compared with that during the same period last year, ρ(PM2.5) of each region decreased by 3.9 µg·m-3, 3.3 µg·m-3, and 1.4 µg·m-3 due to the contribution of the improvement in the pollution meteorological conditions, which is nearly 58.5% on average of the total decrease in PM2.5 concentration. However, the change in O3 pollution meteorological conditions was better in the north and worse in the south, and the overall deterioration in the Yangtze River Delta Region led to approximately 2.8 µg·m-3 growth for the O3 concentration. The PM2.5 and O3 concentrations after excluding the impact of meteorological differences showed different distribution characteristics from the air quality monitoring, in which the high concentrations of PM2.5 were distributed along the Bohai Sea, the inter-provincial border, and the south of the region, whereas the high concentrations of O3 were concentrated along the Taihang Mountains, around Mount Tai, and in parts of the Yangtze River Delta. The daily concentration variations in a single city during a specific pollution control period could be used as a basis for evaluating the effectiveness of local supervision and control, which will provide a reference for the dynamic supervision and daily scheduling of local control management.

10.
Int J Mol Sci ; 24(24)2023 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-38139148

RESUMEN

Bcl2l1 (Bcl-XL) belongs to the Bcl-2 family, Bcl2 and Bcl2-XL are major anti-apoptotic proteins, and the apoptosis of osteoblasts is a key event for bone homeostasis. As the functions of Bcl2l1 in osteoblasts and bone homeostasis remain unclear, we generated osteoblast-specific Bcl2l1-deficient (Bcl2l1fl/flCre) mice using 2.3-kb Col1a1 Cre. Trabecular bone volume and the trabecular number were lower in Bcl2l1fl/flCre mice of both sexes than in Bcl2l1fl/fl mice. In bone histomorphometric analysis, osteoclast parameters were increased in Bcl2l1fl/flCre mice, whereas osteoblast parameters and the bone formation rate were similar to those in Bcl2l1fl/fl mice. TUNEL-positive osteoblastic cells and serum TRAP5b levels were increased in Bcl2l1fl/flCre mice. The deletion of Bcl2l1 in osteoblasts induced Tnfsf11 expression, whereas the overexpression of Bcl-XL had no effect. In a co-culture of Bcl2l1-deficient primary osteoblasts and wild-type bone-marrow-derived monocyte/macrophage lineage cells, the numbers of multinucleated TRAP-positive cells and resorption pits increased. Furthermore, serum deprivation or the deletion of Bcl2l1 in primary osteoblasts increased apoptosis and ATP levels in the medium. Therefore, the reduction in trabecular bone in Bcl2l1fl/flCre mice may be due to enhanced bone resorption through osteoblast apoptosis and the release of ATP from apoptotic osteoblasts, and Bcl2l1 may inhibit bone resorption by preventing osteoblast apoptosis.


Asunto(s)
Resorción Ósea , Osteogénesis , Animales , Femenino , Masculino , Ratones , Adenosina Trifosfato/metabolismo , Apoptosis/genética , Proteína bcl-X/genética , Proteína bcl-X/metabolismo , Resorción Ósea/genética , Resorción Ósea/metabolismo , Hueso Esponjoso/metabolismo , Diferenciación Celular , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
11.
Eur J Phys Rehabil Med ; 59(6): 660-668, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37869761

RESUMEN

BACKGROUND: Robotic training with high repetitions facilitates upper-limb movements but provides fewer benefits for activities of daily living. Integrating activities of daily living training tasks and mirror therapy into a robot may enhance the functional gains of robotic training. AIM: The aim of this study was to investigate the feasibility, safety, and efficacy of the task-oriented mirrored upper-limb robotic training on the upper-limb functions and activities of daily living of subacute poststroke patients. DESIGN: This study is a single-blinded, active-controlled pilot study. SETTING: The study was carried out at rehabilitation outpatient clinic and ward. POPULATION: A total of 32 subacute poststroke patients were enrolled in the study. METHODS: The enrolled patients were allocated into two groups in a ratio of 1:1. The experimental group received 4 weeks of task-oriented mirrored upper-limb robotic training, consisting of five sessions of 30-minute duration, along with 30 minutes of conventional training. The control group only received 60 minutes of conventional training. The outcome measures were the Fugl-Meyer Assessment Scale for Upper Extremity, Modified Barthel Index, Stroke Self-Efficacy Scale, System Usability Scale, and Quebec User Evaluation with Assistive Technology. RESULTS: All patients completed the full training sessions without significant adverse events related to robotic training. The task-oriented mirrored upper-limb robotic training led to increased Fugl-Meyer Assessment Scale for Upper Extremity (difference: 10.38 points, P<0.001) and Modified Barthel Index (difference: 18.38 points, P<0.001) scores, both of which exceeded the minimal clinically important difference. Intergroup analysis showed significantly higher improvements in the Fugl-Meyer Assessment Scale for Upper Extremity total scores, shoulder, wrist, and hand scores; and Modified Barthel Index scores in the experimental group than in conventional training (all P<0.05). Both groups showed significant improvements in Stroke Self-Efficacy Scale scores after the intervention (both P<0.001), but without a statistically significant intergroup difference (P>0.05). Participants in the experimental group scored an average usability perception score of 74.74 (good) and an average satisfaction score of four or more out of five. CONCLUSIONS: In general, task-oriented mirrored upper-limb robotic training appears feasible and safe for subacute poststroke rehabilitation, facilitating the recovery of upper-limb functions and activities of daily living. CLINICAL REHABILITATION IMPACT: Task-oriented mirrored upper-limb robotic training shows promise for future clinical rehabilitation and clinical trials involving subacute poststroke patients.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Actividades Cotidianas , Estudios de Factibilidad , Proyectos Piloto , Recuperación de la Función , Resultado del Tratamiento , Extremidad Superior
12.
Artículo en Inglés | MEDLINE | ID: mdl-37882603

RESUMEN

The power conversion efficiency (PCE) of perovskite solar cells has improved quickly in the past few years, but the PCE is still much lower than the theoretical limit. The relatively high energy loss (Eloss) is one of the critical factors limiting the PCE. To resolve the above issues, a synergistic modification strategy was used herein to minimize Eloss. RbCl and potassium polyacrylate (K-PAM) were used to modify the SnO2 layer. Additionally, Pb(Ac)2 was introduced into PbI2 to further improve the film quality. The synergistic modification strategy reduced the defects in SnO2 and perovskite and improved the energy-level alignment, enabling significantly reduced Eloss and enhanced photovoltaic performance. The best PCE of 24.07% was achieved, which was much higher than that of the control device (20.86%). The Eloss was only 0.349 eV for the target device. Good stability was achieved for the cells made using modified SnO2 and perovskite layers.

13.
Artículo en Inglés | MEDLINE | ID: mdl-37883252

RESUMEN

Existing image inpainting methods often produce artifacts that are caused by using vanilla convolution layers as building blocks that treat all image regions equally and generate holes at random locations with equal probability. This design does not differentiate the missing regions and valid regions in inference and does not consider the predictability of missing regions in training. To address these issues, we propose a deformable dynamic sampling (DDS) mechanism which is built on deformable convolutions (DCs), and a constraint is proposed to avoid the deformably sampled elements falling into the corrupted regions. Furthermore, to select both valid sample locations and suitable kernels dynamically, we equip DCs with content-aware dynamic kernel selection (DKS). In addition, to further encourage the DDS mechanism to find meaningful sampling locations, we propose to train the inpainting model with mined predictable regions as holes. During training, we jointly train a mask generator with the inpainting network to generate hole masks dynamically for each training sample. Thus, the mask generator can find large yet predictable missing regions as a better alternative to random masks. Extensive experiments demonstrate the advantages of our method over state-of-the-art methods qualitatively and quantitatively.

14.
Folia Neuropathol ; 61(3): 326-335, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37818693

RESUMEN

As of now, there are no satisfactory treatments for spinal cord injury (SCI), so new therapeutic approaches are necessary to be explored. Adipose-derived mesenchymal stem cell exosomes (ADMSC-Exo), delightfully, show remarkable therapeutic effects. Therefore, we try to investigate the effects and mechanisms of ADMSC-Exo on SCI, as well as to provide novel approaches for the treatment of SCI. Adipose-derived mesenchymal stem cells (ADMSC) were isolated from rats and then exosomes (Exo) were extracted from the cells. The extracted Exo were identified by flow cytometry, transmission electron microscopy and nanoparticle tracking analysis (NTA). Then, the SCI rat model was established by the spinal cord impactor and injected with 200 µl PBS or Exo into their tail veins at 30 min, 24 h, and 48 h after surgery. The rats in the Control group and Exo group only exposed the spine. Motor function recovery was assessed on days 0, 7, 14, 21, and 28; histopathological changes and apoptosis levels in spinal cord tissues were observed by HE staining and TUNEL staining; the levels of inflammatory cytokines TNF-a, IL-6, and MCP-1 in spinal cord tissues were measured by ELISA; the expression levels of iNOS, IL-12, Arg1, and Mrc1 in spinal cord tissues were detected by qRT-PCR; and Nrf2, HO-1, and NQO1 protein expression in spinal cord tissues were detected by Western blot. ADMSC-Exo were successfully isolated and identified. ADMSC-Exo significantly relieved SCI and promoted motor function recovery in SCI rats. Moreover, ADMSC-Exo inhibited the expression of both inflammatory factors in the spinal cord tissues and M1 microglia, promoted the expression of M2 microglia, and activated the Nrf2/HO-1 pathway. Altogether, ADMSC-Exo can not only ameliorate SCI, but also promote the motor function recovery of rats. And the mechanism of ADMSC-Exo improving SCI may be achieved by activating Nrf2/HO-1 pathway and microglial polarization.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Animales , Ratas , Exosomas/metabolismo , Exosomas/patología , Células Madre Mesenquimatosas/metabolismo , Microglía/metabolismo , Factor 2 Relacionado con NF-E2 , Médula Espinal/patología , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/patología
15.
Artículo en Inglés | MEDLINE | ID: mdl-37713223

RESUMEN

Existing works mainly focus on crowd and ignore the confusion regions which contain extremely similar appearance to crowd in the background, while crowd counting needs to face these two sides at the same time. To address this issue, we propose a novel end-to-end trainable confusion region discriminating and erasing network called CDENet. Specifically, CDENet is composed of two modules of confusion region mining module (CRM) and guided erasing module (GEM). CRM consists of basic density estimation (BDE) network, confusion region aware bridge and confusion region discriminating network. The BDE network first generates a primary density map, and then the confusion region aware bridge excavates the confusion regions by comparing the primary prediction result with the ground-truth density map. Finally, the confusion region discriminating network learns the difference of feature representations in confusion regions and crowds. Furthermore, GEM gives the refined density map by erasing the confusion regions. We evaluate the proposed method on four crowd counting benchmarks, including ShanghaiTech Part_A, ShanghaiTech Part_B, UCF_CC_50, and UCF-QNRF, and our CDENet achieves superior performance compared with the state-of-the-arts.

16.
J Pharm Anal ; 13(6): 616-624, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37440907

RESUMEN

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted.

17.
IEEE Trans Image Process ; 32: 3108-3120, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37220043

RESUMEN

Both salient object detection (SOD) and camouflaged object detection (COD) are typical object segmentation tasks. They are intuitively contradictory, but are intrinsically related. In this paper, we explore the relationship between SOD and COD, and then borrow successful SOD models to detect camouflaged objects to save the design cost of COD models. The core insight is that both SOD and COD leverage two aspects of information: object semantic representations for distinguishing object and background, and context attributes that decide object category. Specifically, we start by decoupling context attributes and object semantic representations from both SOD and COD datasets through designing a novel decoupling framework with triple measure constraints. Then, we transfer saliency context attributes to the camouflaged images through introducing an attribute transfer network. The generated weakly camouflaged images can bridge the context attribute gap between SOD and COD, thereby improving the SOD models' performances on COD datasets. Comprehensive experiments on three widely-used COD datasets verify the ability of the proposed method. Code and model are available at: https://github.com/wdzhao123/SAT.

18.
J Environ Manage ; 338: 117843, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-37004485

RESUMEN

Wet air oxidation (WAO) is a clean and eco-friendly technology for dyes removal, but the high operating temperature and pressure limit its practical application. In the present work, an electric field-promoting (EF-promoting) catalytic WAO process is developed to degrade dyes under room condition. The oxidation kinetics of four different types of dyes and their degradation pathways are studied. A kinetic model is constructed by including the exogenous electric field into the Langmuir-Hinshelwood-Hougen-Watson (LHHW) mechanism framework, and quantitative structure-activity relationship (QSAR) analysis is conducted to correlate the kinetic parameters to the physicochemical properties of the dyes. A negative linear relationship is found between the adsorption equilibrium constants of the dyes and their first ionization energies, and their surface reaction rate constants are positively linearly associated to Esum (ELUMO + EHOMO). The degradation pathways of the different dyes are proposed according to the degradation intermediates and the activities of the atoms within the dye molecules. The heteroatoms N and S, and the atom C connecting the aromatic rings are identified as the susceptible sites upon the electrophilic attack of O2. Bond cleavage at these sites gives rise to aromatic fragments which are eventually mineralized via carboxyl acids. The results of this work is helpful for guiding the design and operation of the EF-promoting catalytic WAO process into the treatment of various dye wastewaters.


Asunto(s)
Colorantes , Contaminantes Químicos del Agua , Cinética , Colorantes/química , Oxidación-Reducción , Aguas Residuales , Catálisis , Contaminantes Químicos del Agua/química
19.
Mol Cancer Ther ; 22(6): 778-789, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36995981

RESUMEN

Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-complement factor H (CFH) autoantibodies in patients with lung cancer that were associated with early-stage disease and exceptional outcomes. The human mAb GT103, produced from a single CFH autoantibody-expressing B cell of a patient with lung cancer, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. Recent experiments have shown that GT103 restructures the tumor microenvironment and initiates a robust antitumoral adaptive immune response. The current study further elucidates several mechanisms by which GT103 kills tumor cells and drives the immune program. Here we show GT103 has specificity for tumor cells without binding to native soluble CFH or normal tissues. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger-associated molecular pattern molecule calreticulin to the plasma membrane. We also demonstrate that GT103 causes B-cell activation in vitro and in vivo, and that GT103 antitumor activity in vivo is B-cell dependent. The complex mechanism of GT103, a tumor-specific antibody that kills tumor cells and stimulates an immune response, supports further development of this human-derived antibody as a novel therapeutic option for patients with lung cancer.


Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Animales , Humanos , Factor H de Complemento/uso terapéutico , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Pulmonares/patología , Autoanticuerpos/uso terapéutico , Antineoplásicos/uso terapéutico , Microambiente Tumoral
20.
J Invest Dermatol ; 143(5): 699-710.e10, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36528128

RESUMEN

Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor SNAI1 is overexpressed in the epidermis of patients with systemic sclerosis, and a transgenic mouse recapitulating this expression pattern is sufficient to induce many clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin (SPON2) in fibrogenesis. Mindin is produced by SNAI1 transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.


Asunto(s)
Fibroblastos , Esclerodermia Sistémica , Ratones , Animales , Humanos , Fibroblastos/metabolismo , Esclerodermia Sistémica/patología , Piel/patología , Proteínas de la Matriz Extracelular/metabolismo , Fibrosis , Ratones Transgénicos , Modelos Animales de Enfermedad , Proteínas de Neoplasias/metabolismo
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