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1.
Adv Mater ; : e2407492, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39118571

RESUMO

The introduction of abundant metals to form ternary germanium-based chalcogenides can dilute the high price and effectively buffer the volume variation of germanium. Herein, olivine-structured Fe2GeX4 (X = S, Se, and Te) are synthesized by a chemical vapor transport method to compare their sodium storage properties. A series of in situ and ex situ measurements validate a combined intercalation-conversion-alloying reaction mechanism of Fe2GeX4. Fe2GeS4 exhibits a high capacity of 477.9 mA h g-1 after 2660 cycles at 8 A g-1, and excellent rate capability. Furthermore, the Na3V2(PO4)3//Fe2GeS4 full cell delivers a capacity of 375.5 mA h g-1 at 0.5 A g-1, which is more than three times that of commercial hard carbon, with a high initial Coulombic efficiency of 93.23%. Capacity-contribution and kinetic analyses reveal that the alloying reaction significantly contributes to the overall capacity and serves as the rate-determining step within the reaction for both Fe2GeS4 and Fe2GeSe4. Upon reaching a specific cycle threshold, the assessment of the kinetic properties of Fe2GeX4 primarily relies on the ion diffusion process that occurs during charging. This work demonstrates that Fe2GeX4 possesses promising practical potential to outperform hard carbon, offering valuable insights and impetus for the advancement of ternary germanium-based anodes.

2.
Discov Oncol ; 15(1): 327, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090431

RESUMO

Small cell lung cancer (SCLC) is an extremely aggressive cancer with a relatively low median survival rate after diagnosis. Treatment options such as chemotherapy or combination immunotherapy have shown clinical benefits, but resistance and relapse can occur. Antibody-drug conjugates (ADCs), as a novel class of biopharmaceutical compounds, have broad application prospects in the treatment of SCLC. ADCs consist of monoclonal antibodies that specifically target cancer cells and are attached to cytotoxic drugs, allowing for targeted killing of cancer cells while sparing healthy tissues. Current clinical studies focus on Delta-like protein 3 (DLL3), CD56, Trophoblast cell surface antigen 2 (Trop-2), B7-H3, and SEZ6. Although toxicities exceeding expectations have been observed with Rova-T, drugs targeting TROP-2 (Sacituzumab Govitecan), B7-H3 (DS-7300), and SEZ6 (ABBV-011) have shown exciting clinical benefits. In this review, we collect the latest clinical evidence to describe the therapeutic efficacy and safety of ADCs in SCLC and discuss prospects and challenges.

3.
Eur J Pharmacol ; 981: 176866, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089461

RESUMO

RATIONALE: The rewarding effect of Methamphetamine (METH) is commonly believed to play an important role in METH use disorder. The altered expression of dopamine D1 receptor (D1R) has been suggested to be essential to the rewarding effect of METH. Notably, D1R could interact with histamine H3 receptors (H3R) by forming a H3R-D1R heteromer (H3R-D1R). OBJECTIVES: This study was designed to specifically investigate the involvement of H3R-D1R in the rewarding effect of METH. METHODS: C57BL/6 mice were treated with intraperitoneal injections of a selective H3R antagonist (Thioperamide, THIO; 20 mg/kg), an H1R antagonist (Pyrilamine, PYRI; 10 mg/kg), or microinjections of cytomegalovirus (CMV)-transmembrane domain 5 (TM5) into the nucleus accumbens (NAc). The animal model of Conditioned Place Preference (CPP) was applied to determine the impact of H3R-D1R on the rewarding effect of METH. RESULTS: METH resulted in a significant preference for the drug-associated chamber, in conjunction with increased H3R and decreased D1R expression in both NAc and the ventral tegmental area (VTA). THIO significantly attenuated the rewarding effect of METH, accompanied by decreased H3R and increased D1R expression. In contrast, pyrilamine failed to produce the similar effects. Moreover, the inhibitory effect of THIO on METH-induced CPP was reversed by SKF38393, a D1R agonist. Furthermore, SCH23390, a D1R antagonist, counteracted the ameliorative effect of SKF38393 on THIO. Co-immunoprecipitation (CO-IP) experiments further demonstrated the specific interaction between H3R and D1R in METH CPP mice. The rewarding effect of METH was also significantly blocked by the interruption of CMV-transmembrane domain 5 (TM5), but not CMV-transmembrane domain 7 (TM7) in NAc. CONCLUSION: These results suggest that modulating the activity of H3R-D1R complex holds promise for regulating METH use disorder and serves as a potential drug target for its treatment.

4.
BMC Pediatr ; 24(1): 524, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138576

RESUMO

BACKGROUND: Nonsuicidal self-injury (NSSI) is a serious problem in the adolescent population worldwide. Childhood trauma and bullying have been identified as risk factors for NSSI. We explored the relationships among Childhood trauma, Bullying victimization and the severity of NSSI behaviours, and test the effect of Bullying victimization in mediating the association between Childhood trauma and the NSSI behaviours. METHODS: A total of 123 adolescents were recruited. They were diagnosed with depression or depressive episodes of bipolar disorder and had experienced NSSI in the last year. They were assessed using the Chinese version of the Childhood Trauma Questionnaire (CTQ-C), the Revised Olweus Bullying Victimization Questionnaire (OBVQ-R), and the Adolescent Self-Harm Questionnaire (ASHQ). RESULTS: Females presented a significantly greater prevalence of sexual abuse and relationship bullying than boys. Individuals in the younger age group (10-14 years) presented a greater incidence of emotional neglect, verbal bullying, relationship bullying, and total bullying, and their NSSI score was also higher than that of those in the older age group (15-19 years). Only children show a greater prevalence of sexual abuse than nononly children. Single-parent families scored higher on emotional abuse, emotional neglect, physical neglect and physical bullying than two-parent families. There was a significant positive correlation between each dimension of childhood trauma and all the dimensions of bullying, between childhood trauma and NSSI, and between bullying and NSSI. Childhood trauma can not only directly affect the severity of NSSI but also indirectly aggravate the severity of NSSI through bullying victimization. The mediating effects of bullying victimization on emotional abuse, physical abuse, emotional neglect and physical neglect were 14%, 21%, 20%, 13% and 20%, respectively. CONCLUSION: There was a significant positive correlation between childhood trauma and bullying, between childhood trauma and NSSI, and between bullying and NSSI. Childhood trauma can not only directly affect the severity of NSSI but also indirectly aggravate the severity of NSSI through bullying victimization. Bullying victimization played the partial mediating effects between Childhood trauma and NSSI.


Assuntos
Bullying , Vítimas de Crime , Comportamento Autodestrutivo , Humanos , Adolescente , Bullying/psicologia , Masculino , Feminino , Criança , Vítimas de Crime/psicologia , Comportamento Autodestrutivo/psicologia , Comportamento Autodestrutivo/epidemiologia , Experiências Adversas da Infância/psicologia , Fatores de Risco , Adulto Jovem , Maus-Tratos Infantis/psicologia , China/epidemiologia , Prevalência , Inquéritos e Questionários
5.
Opt Lett ; 49(15): 4413-4416, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090947

RESUMO

Lobster eye x ray micro pore optics (MPO) is a novel bionic optical technology with a unique microchannel structure. All square microchannels point to the same spherical center position, providing a wide field of view and high focusing and imaging capabilities. Enhancing the optical performance of MPO has been a significant challenge. This study introduces what we believe is a novel approach using a stiffener and staggered-square honeycomb structure design to enhance the optical properties of the MPO devices. The x ray test results show that the multifiber stiffener design enhances optical quality by approximately 20% during the melt pressing stage. The staggered-square honeycomb structure design reduces channel errors by nearly 67% in the thermal forming and coating stage. Consequently, the angular resolution of the MPO has been significantly enhanced, reducing from 4.25 to 2.68 arc min. This innovative structure design shows promise for enhancing lobster eye optics performance and has potential applications in the related field.

6.
J Transl Med ; 22(1): 665, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020378

RESUMO

Metastatic breast cancer (mBC) poses a significant threat to women's health and is a major cause of malignant neoplasms in women. Human epidermal growth factor receptor (HER)3, an integral member of the ErbB/HER receptor tyrosine kinase family, is a crucial activator of the phosphoinositide-3 kinase/protein kinase B signaling pathway. HER3 overexpression significantly contributes to the development of resistance to drugs targeting other HER receptors, such as HER2 and epidermal growth factor receptors, and plays a crucial role in the onset and progression of mBC. Recently, numerous HER3-targeted therapeutic agents, such as monoclonal antibodies (mAbs), bispecific antibodies (bAbs), and antibody-drug conjugates (ADCs), have emerged. However, the efficacy of HER3-targeted mAbs and bAbs is limited when used individually, and their combination may result in toxic adverse effects. On the other hand, ADCs are cytotoxic to cancer cells and can bind to target cells through antibodies, which highlights their use in targeted HER3 therapy for mBC. This review provides an overview of recent advancements in HER3 research, historical initiatives, and innovative approaches in targeted HER3 therapy for metastatic breast cancer. Evaluating the advantages and disadvantages of current methods may yield valuable insights and lessons.


Assuntos
Neoplasias da Mama , Metástase Neoplásica , Receptor ErbB-3 , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-3/metabolismo , Receptor ErbB-3/antagonistas & inibidores , Feminino , Animais
7.
Dalton Trans ; 53(31): 13055-13064, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39034712

RESUMO

Two-dimensional (2D) semiconductors with suitable band gaps, high carrier mobility, and environmental stability are crucial for applications in the next generation of electronics and optoelectronics. However, current candidate materials each have one or more issues. In this work, two novel C3N2 monolayers, P-C3N2 and I-C3N2 are proposed by first-principles calculations. Both structures have demonstrated excellent dynamical and mechanical stability, with thermal stability approaching 3000 K. Importantly, P-C3N2 shows a distinct advantage in formation energy compared to currently synthesized 2D carbon nitride materials, indicating its potential for experimental synthesis. Electronic structure calculations reveal that both P-C3N2 and I-C3N2 are intrinsic semiconductors with moderate band gaps of 2.19 and 1.81 eV, respectively. Additionally, both C3N2 monolayers display high absorption coefficients up to 105 cm-1, with P-C3N2 showing significant absorption capabilities in the visible light region. Remarkably, P-C3N2 possesses an ultra-high carrier mobility of up to 104 cm2 V-1 s-1. These findings provide theoretical insights and candidates for future applications in the electronics and optoelectronics fields.

8.
Opt Express ; 32(11): 18744-18745, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859024

RESUMO

An erratum to correct a mistake for the article titled "Staring X-ray backscatter imaging based on ultra-high aspect ratio lobster eye lens" published in Opt. Express32(7), 11600 (2024)10.1364/OE.514941. The corrections have no influence on the results and conclusions of the original paper.

9.
Br J Ophthalmol ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839251

RESUMO

BACKGROUND/AIMS: The aim of this study was to develop and evaluate digital ray, based on preoperative and postoperative image pairs using style transfer generative adversarial networks (GANs), to enhance cataractous fundus images for improved retinopathy detection. METHODS: For eligible cataract patients, preoperative and postoperative colour fundus photographs (CFP) and ultra-wide field (UWF) images were captured. Then, both the original CycleGAN and a modified CycleGAN (C2ycleGAN) framework were adopted for image generation and quantitatively compared using Frechet Inception Distance (FID) and Kernel Inception Distance (KID). Additionally, CFP and UWF images from another cataract cohort were used to test model performances. Different panels of ophthalmologists evaluated the quality, authenticity and diagnostic efficacy of the generated images. RESULTS: A total of 959 CFP and 1009 UWF image pairs were included in model development. FID and KID indicated that images generated by C2ycleGAN presented significantly improved quality. Based on ophthalmologists' average ratings, the percentages of inadequate-quality images decreased from 32% to 18.8% for CFP, and from 18.7% to 14.7% for UWF. Only 24.8% and 13.8% of generated CFP and UWF images could be recognised as synthetic. The accuracy of retinopathy detection significantly increased from 78% to 91% for CFP and from 91% to 93% for UWF. For retinopathy subtype diagnosis, the accuracies also increased from 87%-94% to 91%-100% for CFP and from 87%-95% to 93%-97% for UWF. CONCLUSION: Digital ray could generate realistic postoperative CFP and UWF images with enhanced quality and accuracy for overall detection and subtype diagnosis of retinopathies, especially for CFP.\ TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT05491798).

10.
Opt Express ; 32(7): 11600-11612, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571003

RESUMO

In contrast to conventional X-ray imaging systems, the lobster eye lens, serving as a pivotal component for X-ray focusing, presents the potential for downsizing X-ray backscatter imaging systems. This study reports the successful implementation of a pioneering non-contact staring X-ray backscatter imaging experiment, with the target positioned 1.5 meters away from the system and employing a tube voltage of 60 kV for the X-ray light source. The system is built upon a novel high aspect ratio (500) meridian lobster eye lens, employing a laboratory low illuminance desktop light source and a commercial X-ray detector to achieve high-resolution focused imaging of hard X-rays. Point spread function testing and a series of imaging experiments were carried out to assess the resolution and optimal imaging photon energy of the proposed system. Furthermore, according to the characteristics of the point spread function of the cross image of the lobster eye lens, we proposed an image processing algorithm. The experimental results demonstrate that, after processing, the Structural Similarity (SSIM) Index of the backscatter image and the ground truth image can be improved from an average of 0.0526 to 0.5758. Our research significantly contributes to the advancement of a new generation of X-ray backscatter imaging systems.

11.
J Colloid Interface Sci ; 665: 846-854, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38564948

RESUMO

The unique superconductivity and charge density wave transition characteristics of NbSe2 make it worthy of exploring its electrochemical performance and potential applications in the field of batteries. Herein, the bulk NbSe2 was successfully exfoliated into few-layered NbSe2 nanostructures by wet grinding exfoliation approach, which solved the issues of its long activation period and poor cycle stability. The strong Nb-Se bond in the plane and weak van der Waals force between the adjacent layers could render the fast Na+ diffusion, provide abundant reaction sites and multi-directional migration paths, thus accelerate the ionic conductivity. The theoretical calculations verified the high Na+ adsorption tendency between the NbSe2 interlayers stemming from the continuous region of charge accumulation. Thanks to the unique electronic and two-dimensional few-layered structures, the exfoliated NbSe2 exhibited a high cyclic stability with a capacity of 502 mA h g-1 over 2800 cycles at 10 A/g. In addition, the reaction mechanism was studied by in-situ X-ray diffraction and other tests, indicating a reaction mechanism containing of simultaneous intercalation (NbSe2↔NaxNbSe2↔NaNbSe2↔Na1+xNbSe2) and conversion processes in NbSe2. This parallelly running mechanism not only alleviates the volume change but also ensures a high specific capacity. Additionally, different lattice planes of the NaNbSe2 intermediate in the intercalation process experience varying degrees of contraction and expanding in d-spacing due to the influence of Coulombic force.

12.
Int Ophthalmol ; 44(1): 148, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502381

RESUMO

PURPOSE: To investigate corneal biomechanical properties and its associations with the severity of lens dislocation in patients with Marfan syndrome. METHODS: A total of 30 patients with Marfan syndrome and 30 age-, sex- and axial length (AL)-matched controls were recruited. Corneal biomechanical parameters of both groups were measured by CorVis ST and were compared between groups. Potential associations between corneal biomechanical parameters and severity of lens dislocation were also investigated. RESULTS: Lower applanation 1 velocity (A1V) (0.13 ± 0.004 vs. 0.15 ± 0.003, P = 0.016), shorter applanation 2 time (A2T)(22.64 ± 0.11 vs. 22.94 ± 0.11, P = 0.013), longer peak distance (PD) (5.03 ± 0.07 vs. 4.81 ± 0.05, P = 0.008), longer radius (R) of highest concavity (7.44 ± 0.16 vs. 6.93 ± 0.14, P = 0.012), greater Ambrosio relational thickness horizontal (ARTh) (603 ± 20 vs. 498 ± 12, P < 0.001), and integrated radius (IR) (8.32 ± 0.25 vs. 8.95 ± 0.21, P = 0.033) were detected among Marfan eyes compared with controls (all P < 0.05). Marfan individuals with more severe lens dislocation tended to have increased stiffness parameter as longer A1T, slower A1V, shorter A2T, slower application 2 velocity (A2V), smaller PD and smaller Distance Amplitude (DA) (P < 0.05). CONCLUSION: Marfan patients were detected to have increased corneal stiffness compared with normal subjects. Corneal biomechanical parameters were significantly associated with the severity of lens dislocation in Marfan patients.


Assuntos
Subluxação do Cristalino , Síndrome de Marfan , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Pressão Intraocular , Fenômenos Biomecânicos , Córnea , Subluxação do Cristalino/diagnóstico , Subluxação do Cristalino/etiologia , Tonometria Ocular
13.
Phys Chem Chem Phys ; 26(7): 6292-6299, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305764

RESUMO

Two-dimensional material-supported single metal atom catalysts have been extensively studied and proved effective in electrocatalytic reactions in recent years. In this work, we systematically investigate the OER catalytic properties of single metal atoms supported by the NiN2 monolayer. Several typical transition metals with high single atom catalytic activity, such as Fe, Co, Ru, Rh, Pd, Ir, and Pt, were selected as catalytic active sites. The energy calculations show that transition metal atoms (Fe, Co, Ru, Rh, Pd, Ir, and Pt) are easily embedded in the NiN2 monolayer with Ni vacancies due to the negative binding energy. The calculated OER overpotentials of Fe, Co, Ru, Rh, Pd, Ir and Pt embedded NiN2 monolayers are 0.92 V, 0.47 V, 1.13 V, 0.66 V, 1.25 V, 0.28 V, and 0.94 V, respectively. Compared to the 0.57 V OER overpotential of typical OER noble metal catalysts IrO2, Co@NiN2 and Ir@NiN2 exhibit high OER catalytic activity due to lower overpotential, especially for Ir@NiN2. The high catalytic activity of the Ir embedded NiN2 monolayer can be explained well by the d-band center model. It is found that the adsorption strength of the embedded TM atoms with intermediates follows a linear relationship with their d-band centers. Besides, the overpotential of the Ir embedded NiN2 monolayer can be further reduced to 0.24 V under -2% biaxial strain. Such findings are expected to be employed in more two-dimensional material-supported single metal atom catalyzed reactions.

14.
Acta Biochim Biophys Sin (Shanghai) ; 56(4): 551-563, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38404180

RESUMO

Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis. Subsequently, the AKI mouse model is induced by administering a single dose of CDDP via intraperitoneal injection. By detecting the serum urea nitrogen and creatinine levels, as well as the histopathological changes, we confirm that agrimol B effectively reduces CDDP-induced AKI. In addition, treatment with agrimol B counteracts the increase in renal malondialdehyde level and the decrease in superoxide dismutase (SOD), catalase and glutathione levels induced by CDDP. Moreover, western blot results reveal that agrimol B upregulates the expressions of Sirt1, SOD2, nuclear factor erythroid2-related factor 2, and downstream molecules, including heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1. However, administration of the Sirt1 inhibitor EX527 abolishes the effects of agrimol B. Finally, we establish a tumor-bearing mouse model and find that agrimol B has a synergistic antitumor effect with CDDP. Overall, agrimol B attenuates CDDP-induced AKI by activating the Sirt1/Nrf2 signaling pathway to counteract oxidative stress, suggesting that this compound is a potential therapeutic agent for the treatment of CDDP-induced AKI.


Assuntos
Injúria Renal Aguda , Butanonas , Cisplatino , Fenóis , Camundongos , Animais , Cisplatino/toxicidade , Sirtuína 1/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Transdução de Sinais , Rim/metabolismo , Estresse Oxidativo
15.
Plant Sci ; 342: 112034, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38365003

RESUMO

Transcription factors are central components in cell signal transduction networks and are critical regulators for gene expression. It is estimated that approximately 10% of all transcription factors are membrane-tethered. MTFs (membrane-bound transcription factors) are latent transcription factors that are inherently anchored in the cellular membrane in a dormant form. When plants encounter environmental stimuli, they will be released from the membrane by intramembrane proteases or by the ubiquitin proteasome pathway and then were translocated to the nucleus. The capacity to instantly activate dormant transcription factors is a critical strategy for modulating diverse cellular functions in response to external or internal signals, which provides an important transcriptional regulatory network in response to sudden stimulus and improves plant survival. NTLs (NTM1-like) are a small subset of NAC (NAM, ATAF1/2, CUC2) transcription factors, which contain a conserved NAC domain at the N-terminus and a transmembrane domain at the C-terminus. In the past two decades, several NTLs have been identified from several species, and most of them are involved in both development and stress response. In this review, we review the reports and findings on NTLs in plants and highlight the mechanism of their nuclear import as well as their functions in regulating plant growth and stress response.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Membrana/metabolismo , Membrana Celular/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico
16.
Curr Cancer Drug Targets ; 24(9): 910-919, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38279718

RESUMO

Leptomeningeal metastasis (LM) is a serious and often fatal complication in patients with advanced lung cancer, resulting in significant neurological deficits, decreased quality of life, and a poor prognosis. This article summarizes current research advances in treating lung cancer with meningeal metastases, discusses clinical challenges, and explores treatment strategies. Through an extensive review of relevant clinical trial reports and screening of recent conference abstracts, we collected clinical data on treating patients with lung cancer with meningeal metastases to provide an overview of the current research progress. Exciting progress has been made by focusing on specific mutations within lung cancer, including the use of EGFR tyrosine kinase inhibitors or inhibitors for anaplastic lymphoma kinase gene rearrangement, such as osimertinib, alectinib, and lorlatinib. These targeted therapies have shown impressive results in penetrating the central nervous system (CNS). Regarding whole-brain radiotherapy, there is currently some controversy among investigators regarding its effect on survival. Additionally, immune checkpoint inhibitors (ICIs) have demonstrated reliable clinical benefits due to their ability to retain anticancer activity in CNS metastases. Moreover, combination therapy shows promise in providing further treatment possibilities. Considerable progress has been made in the clinical research of lung cancer with LM. However, the sample size of prospective clinical trials investigating LM for lung cancer is still limited, with most reports being retrospective. Developing more effective management protocols for metastatic LM in lung cancer remains an ongoing challenge for the future.


Assuntos
Neoplasias Pulmonares , Neoplasias Meníngeas , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular/tendências , Radioterapia/mortalidade , Radioterapia/tendências , Imunoterapia/tendências , Terapia Combinada/tendências , Humanos
17.
Geroscience ; 46(2): 2697-2714, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38153666

RESUMO

Age-related macular degeneration (AMD) is the leading cause of irreversible vision damage among elderly individuals. There is still no efficient treatment for dry AMD. Retinal pigment epithelial (RPE) degeneration has been confirmed to play an important role in dry AMD. Recent studies have reported that ferroptosis caused by iron overload and lipid peroxidation may be the primary causes of RPE degeneration. However, the upstream regulatory molecules of RPE ferroptosis remain largely unknown. Pigment epithelium-derived factor (PEDF) is an important endogenic protective factor for the RPE. Our results showed that in the murine dry AMD model induced by sodium iodate (SI), PEDF expression was downregulated. Moreover, dry AMD-like pathology was observed in PEDF-knockout mice. Therefore, the aim of this study was to reveal the effects and mechanism of PEDF on RPE ferroptosis and investigate potential therapeutic targets for dry AMD. The results of lipid peroxidation and transmission electron microscope showed that retinal ferroptosis was significantly activated in SI-treated mice and PEDF-knockout mice. Restoration of PEDF expression ameliorated SI-induced retinal dysfunction in mice, as assessed by electroretinography and optical coherence tomography. Mechanistically, western blotting and immunofluorescence analysis demonstrated that the overexpression of PEDF could upregulate the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain-1 (FTH1), which proved to inhibit lipid peroxidation and RPE ferroptosis induced by SI. This study revealed the novel role of PEDF in ferroptosis inhibition and indicated that PEDF might be a potential therapeutic target for dry AMD.


Assuntos
Proteínas do Olho , Ferroptose , Fatores de Crescimento Neural , Epitélio Pigmentado da Retina , Serpinas , Humanos , Camundongos , Animais , Idoso , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Modelos Animais de Doenças , Camundongos Knockout
18.
Heliyon ; 10(1): e22913, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38148793

RESUMO

Objective: Exploring the clinical efficacy of camrelizumab in combination with first-line chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC). Methods: The clinical data of 35 patients with ES-SCLC who received camrelizumab combined with EC or EP regimen in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to January 2023 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were OS, ORR and DCR. SPSS 25.0 software was used for statistical analysis, Kaplan-Meier curve and Log-Rank test analysis, and survival curve was drawn. Results: The median PFS of 35 patients with SCLC was 7.4 months (95 % CI 6.75-9.81 months), .and the median OS was 12.5 months (95% CI,11.71-16.90 months). The ORR and DCR were 65.7 % and 74.3 %, respectively. Adverse events (AEs) were mainly concentrated in grade 1-2, and the probability of occurrence of grade 3 or above was low. Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) was the most common, followed by nausea &vomit and anemia. The other common AEs included abnormal thyroid function, decreased neutrophil count, skin rash and leucopenia. Conclusion: Camrelizumab in combination with first-line chemotherapy regimens prolonged OS and PFS in SCLC patients and showed efficacy and safety in real-world data.

19.
Macromol Rapid Commun ; 45(7): e2300650, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38158795

RESUMO

Double-network hydrogels based on calcium alginate are extensively exploited. Unfortunately, their low strength and unstable constitution to open environments limit their application potential. Herein, a new type of double-network organohydrogel (OHG) is proposed. By solvent exchange, a stable physical network is established based on dimethyl sulfoxide (DMSO)-alginate in the presence of a polyacrylamide network. The DMSO content endows tunable mechanical properties, with a maximum tensile strength of ≈1.7 MPa. Importantly, the OHG shows much better environmental stability compared to the conventional double-network hydrogels. Due to the reversible association of hydrogen bonds, the OHG possesses some unique properties, including free-shapeability, shape-memory, and self-adhesion, that offers several promising ways to utilize alginate-based gels for wide applications.


Assuntos
Alginatos , Dimetil Sulfóxido , Solventes , Hidrogéis , Ligação de Hidrogênio
20.
Nat Commun ; 14(1): 8090, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062015

RESUMO

The sensory neocortex has been suggested to be a substrate for long-term memory storage, yet which exact single cells could be specific candidates underlying such long-term memory storage remained neither known nor visible for over a century. Here, using a combination of day-by-day two-photon Ca2+ imaging and targeted single-cell loose-patch recording in an auditory associative learning paradigm with composite sounds in male mice, we reveal sparsely distributed neurons in layer 2/3 of auditory cortex emerged step-wise from quiescence into bursting mode, which then invariably expressed holistic information of the learned composite sounds, referred to as holistic bursting (HB) cells. Notably, it was not shuffled populations but the same sparse HB cells that embodied the behavioral relevance of the learned composite sounds, pinpointing HB cells as physiologically-defined single-cell candidates of an engram underlying long-term memory storage in auditory cortex.


Assuntos
Córtex Auditivo , Neocórtex , Masculino , Camundongos , Animais , Córtex Auditivo/fisiologia , Aprendizagem/fisiologia , Memória de Longo Prazo , Neocórtex/fisiologia , Neurônios/fisiologia , Percepção Auditiva/fisiologia
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