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1.
ACS Appl Mater Interfaces ; 16(26): 34001-34009, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961569

ABSTRACT

Ultrafast electron pulses, generated through femtosecond photoexcitation in nanocathode materials, introduce high-frequency characteristics and ultrahigh temporal-spatial resolution to vacuum micro-nano electronic devices. To advance the development of ultrafast electron sources sensitive to polarized light, we propose an ultrafast pulsed electron source based on a vertical few-layer graphene cold cathode. This source exhibits selective electron emission properties for varying polarization angles, with high switching ratios of 277 (at 0°) and 235 (at 90°). The electron emission of the graphene evolves from cosine to sine as the polarization angle increases from 0° to 90°. The variation of electron emission current with polarization angle is intrinsically related to light absorption, local field enhancement, and photothermal conversion efficiency. A physical mechanism model and semiempirical expression were presented to reveal the MPP and PTE mechanisms at different polarization angles. This tunable conversion between mechanisms indicates potential applications in tunable ultrafast optoelectronic devices.

2.
Nano Lett ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38985015

ABSTRACT

Exciton-polaritons, hybrid quasiparticles from the strong coupling of excitons and cavity photons in semiconductor microcavities, offer a platform for exploring quantum coherence and nonlinear optical properties. The unique polariton parametric scattering (PPS) laser is of interest for its potential in quantum technologies and nonlinear devices. However, direct resonant excitation of polaritons in strong-coupling microcavities is challenging. This study proposes an innovative two-photon absorption (TPA) pump mechanism to address this. We observe TPA-driven PPS lasing in a strongly coupled microcavity at room temperature. High K-value exciton injections promote coherent stimulated emission of polariton scattering through intermode channels. Angle-resolved spectra confirm a TPA process, showing evolution from pump-state to signal-state. Hanbury Brown-Twiss measurement of second-order correlation g2(τ) of signal state indicates a phase transition from a classical thermal state to a quantum coherent state. Theoretical modeling provides insights into the physical mechanisms of PPS. Our work advances nonlinear phenomena exploration in strongly coupled light-matter systems, contributing to quantum polaritonics and nonlinear optics.

3.
Mol Neurobiol ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023795

ABSTRACT

Caspase-12 is a caspase family member for which functions in regulating cell death and inflammation have previously been suggested. In this study, we used caspase-12 lacZ reporter mice to elucidate the expression pattern of caspase-12 in order to obtain an idea about its possible in vivo function. Strikingly, these reporter mice showed that caspase-12 is expressed explicitly in Purkinje neurons of the cerebellum. As this observation suggested a function for caspase-12 in Purkinje neurons, we analyzed the brain and behavior of caspase-12 deficient mice in detail. Extensive histological analyses showed that caspase-12 was not crucial for establishing cerebellum structure or for maintaining Purkinje cell numbers. We then performed behavioral tests to investigate whether caspase-12 deficiency affects memory, motor, and psychiatric functions in mice. Interestingly, while the absence of caspase-12 did not affect memory and motor function, caspase-12 deficient mice showed depression and hyperactivity tendencies, together resembling manic behavior. Next, suggesting a possible molecular mechanistic explanation, we showed that caspase-12 deficient cerebella harbored diminished signaling through the brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic-AMP response binding protein axis, as well as strongly enhanced expression of the neuronal activity marker c-Fos. Thus, our study establishes caspase-12 expression in mouse Purkinje neurons and opens novel avenues of research to investigate the role of caspase-12 in regulating psychiatric behavior.

4.
Expert Opin Ther Pat ; 34(8): 593-610, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38946486

ABSTRACT

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.


Subject(s)
Antineoplastic Agents , Drug Design , Focal Adhesion Protein-Tyrosine Kinases , Neoplasms , Patents as Topic , Protein Kinase Inhibitors , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/enzymology , Animals , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship , Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Drug Development , Chemistry, Pharmaceutical , Molecular Targeted Therapy
5.
World J Clin Cases ; 12(20): 4348-4356, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39015932

ABSTRACT

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare anatomical defect of the pituitary gland falling under the spectrum of holoprosencephaly phenotypes. It is characterized by a deficiency in anterior pituitary hormones, such as growth hormone, gonadotropins, and thyroid hormones. Due to the syndrome's rarity and nonspecific manifestations, there is a lack of standardized treatment strategies. Consequently, early diagnosis through imaging and on-time intervention are crucial for improving patients' outcomes. CASE SUMMARY: A 30-year-old man presented with absent secondary sexual characteristics and azoospermia. Laboratory evaluation revealed a deficiency in gonadotropins, while thyroid function was mostly within normal ranges. Magnetic resonance imaging of the pituitary gland showed pituitary stalk agenesis, hypoplasia of the anterior pituitary, and ectopic posterior pituitary, leading to the diagnosis of PSIS. Initially, the patient underwent 6 mo of gonadotropin therapy without significant changes in hormone levels and secondary sexual characteristics. Pulsatile gonadotropin-releasing hormone therapy was then administered, resulting in the detection of sperm in the semen analysis within 3 mo. After 6 mo, routine semen tests showed normal semen quality. The couple faced challenges in conceiving due to abstinence and underwent three cycles of artificial insemination, which was unsuccessful. They also attempted in vitro fertilization, but unfortunately, the woman experienced a miscarriage 10 wk after the embryo transfer. CONCLUSION: Early detection, accurate diagnosis, and timely treatment are crucial in improving the quality of life and fertility of PSIS patients.

6.
Plant Physiol Biochem ; 213: 108824, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38936072

ABSTRACT

Tetrastigma hemsleyanum Diel et Gilg is a perennial herbaceous plant native to subtropical China with multiple medicinal applications. Supplementing with low-density blue light (BL) for 45 days (3 h/day) can not only significantly increase the yields of root tubers but also significantly increase the flavonoid content and its antioxidant activity. The chlorophyll content in the leaves of T. hemsleyanum significantly decreased, but the photosynthetic efficiency significantly increased after reaching the light saturation point. The production rate of superoxide anion radical in the leaves reached the highest peak after 1.5 h in BL and decreased at 3 h. The H2O2 content in the leaves decreased significantly, while the H2O2 content in the root tubers increased significantly at 3 h in BL. The objective of this research was to determine how the scavenging system, including antioxidant enzymes, antioxidants, and flavonoids respond to the oxidative stress induced by BL in root tubers. After exposure to BL, significant differences in the activity of APX and SOD were observed in the leaves and tubers within 3 h. By analyzing the upregulated flavonoids metabolites and key genes in metabolic pathways through the combined analysis of the flavonoid metabolic group and transcriptome in the root tubers, the upregulated accumulation of flavanols was found to be the main reason for the improvement in the antioxidant properties of flavonoids.


Subject(s)
Flavonoids , Light , Plant Tubers , Vitaceae , Flavonoids/metabolism , Vitaceae/metabolism , Plant Tubers/metabolism , Antioxidants/metabolism , Plant Leaves/metabolism , Plant Roots/metabolism , Hydrogen Peroxide/metabolism , Chlorophyll/metabolism , Photosynthesis , Blue Light
7.
Int Immunopharmacol ; 138: 112547, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38943969

ABSTRACT

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.

8.
MedComm (2020) ; 5(7): e607, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38911066

ABSTRACT

In a recent Nature elegant study, Wang et al. identified CD300ld, a novel functionally highly conserved tumor immunosuppressive receptor, highly expressed specifically on polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), as well as a key receptor in the regulation of recruitment and immunosuppressive function of PMN-MDSCs. Targeting CD300ld could remodel the tumor immune microenvironment, resulting in a broad-spectrum anti-tumor effect.

9.
Biosens Bioelectron ; 261: 116484, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38878698

ABSTRACT

γ-Glutamyltranspeptidase (γ-GGT), as a key enzyme, exhibits markedly higher expression levels in tumor cells compared to normal cells. Under normal conditions, γ-GGT activity on the cell membrane is relatively low, but it undergoes a significant upregulation in cancer cells, making it a potential cancer biomarker. Particularly in A549 cells, a prominent cancer cell line, the pronounced upregulation of γ-GGT expression emphasizes its potential as a unique recognition target and a robust marker for A549 cells. This study successfully synthesized a highly selective γ-GGT fluorescent probe, the exhibits commendable sensitivity (LOD = 0.0021U/mL) and selectivity, achieving efficient detection at the cellular level and providing accurate insights into differential expression between normal and cancer cells. The alterations in fluorescence lifetime observed before and after the probe's reaction with γ-GGT serve as a crucial foundation for fluorescence lifetime imaging on living cells. The probe has become a powerful tool for precise localization of tumor cells, particularly demonstrating its capability for specific recognition in A549 cells. Overall, this research highlights the potential of γ-GGT as a target for fluorescent probes, emphasizing its prospects in specific recognition, particularly in A549 cells, with profound implications for advancing early cancer diagnosis and treatment methods.


Subject(s)
Biosensing Techniques , Fluorescent Dyes , Optical Imaging , gamma-Glutamyltransferase , Humans , gamma-Glutamyltransferase/analysis , gamma-Glutamyltransferase/metabolism , Fluorescent Dyes/chemistry , A549 Cells , Biosensing Techniques/methods , Optical Imaging/methods , Biomarkers, Tumor/analysis , Neoplasms/pathology , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging
10.
Lancet Oncol ; 25(7): 901-911, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823410

ABSTRACT

BACKGROUND: Antibody-drug conjugates have promising clinical activity in the treatment of solid tumours. BL-B01D1 is a first-in-class EGFR-HER3 bispecific antibody-drug conjugate. We aimed to assess the safety and preliminary antitumour activity of BL-B01D1 in patients with locally advanced or metastatic solid tumours. METHODS: This first-in-human, open-label, multicentre, dose-escalation and dose-expansion phase 1 trial was conducted in seven hospitals in China, enrolling patients aged 18-75 years (dose escalation; phase 1a) or older than 18 years (dose expansion; phase 1b), with a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 0-1, and histologically or cytologically confirmed locally advanced or metastatic solid tumours that had progressed on current standard treatment. In the phase 1a i3+3 design, patients received intravenous BL-B01D1 at three different schedules: 0·27 mg/kg, 1·5 mg/kg, and 3·0 mg/kg weekly; 2·5 mg/kg, 3·0 mg/kg, and 3·5 mg/kg on days 1 and 8 of each cycle every 3 weeks; or 5·0 mg/kg and 6·0 mg/kg on day 1 of each cycle every 3 weeks. The primary objectives of phase 1a were to identify the safety, maximum tolerated dose, and dose-limiting toxicity. In phase 1b, patients were treated in two schedules: 2·5 and 3·0 mg/kg on days 1 and 8 every 3 weeks, or 4·5, 5·0, and 6·0 mg/kg on day 1 every 3 weeks. The primary objectives of phase 1b were to assess the safety and recommended phase 2 dose of BL-B01D1, and objective response rate was a key secondary endpoint. Safety was analysed in all patients with safety records who received at least one dose of BL-B01D1. Antitumour activity was assessed in the activity analysis set which included all patients who received at least one dose of BL-B01D1 every 3 weeks. This trial is registered with China Drug Trials, CTR20212923, and ClinicalTrials.gov, NCT05194982, and recruitment is ongoing. FINDINGS: Between Dec 8, 2021, and March 13, 2023, 195 patients (133 [65%] men and 62 [32%] women; 25 in phase 1a and 170 in phase 1b) were consecutively enrolled, including 113 with non-small-cell lung cancer, 42 with nasopharyngeal carcinomas, 13 with small-cell lung cancer, 25 with head and neck squamous cell carcinoma, one with thymic squamous cell carcinoma, and one with submandibular lymphoepithelioma-like carcinoma. In phase 1a, four dose-limiting toxicities were observed (two at 3·0 mg/kg weekly and two at 3·5 mg/kg on days 1 and 8 every 3 weeks; all were febrile neutropenia), thus the maximum tolerated dose was reached at 3·0 mg/kg on days 1 and 8 every 3 weeks and 6·0 mg/kg on day 1 every 3 weeks. Grade 3 or worse treatment-related adverse events occurred in 139 (71%) of 195 patients; the most common of which were neutropenia (91 [47%]), anaemia (76 [39%]), leukopenia (76 [39%]), and thrombocytopenia (63 [32%]). 52 (27%) patients had a dose reduction and five (3%) patients discontinued treatment due to treatment-related adverse events. One patient was reported as having interstitial lung disease. Treatment-related deaths occurred in three (2%) patients (one due to pneumonia, one due to septic shock, and one due to myelosuppression). In 174 patients evaluated for activity, median follow-up was 6·9 months (IQR 4·5-8·9) and 60 (34%; 95% CI 27-42) patients had an objective response. INTERPRETATION: Our results suggest that BL-B01D1 has preliminary antitumour activity in extensively and heavily treated advanced solid tumours with an acceptable safety profile. Based on the safety and antitumour activity data from both phase 1a and 1b, 2·5 mg/kg on days 1 and 8 every 3 weeks was selected as the recommended phase 2 dose in Chinese patients. FUNDING: Sichuan Baili Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
Antibodies, Bispecific , ErbB Receptors , Immunoconjugates , Neoplasms , Receptor, ErbB-3 , Humans , Middle Aged , Male , Female , Antibodies, Bispecific/administration & dosage , Antibodies, Bispecific/adverse effects , Antibodies, Bispecific/therapeutic use , Aged , Adult , Neoplasms/drug therapy , Neoplasms/pathology , Immunoconjugates/administration & dosage , Immunoconjugates/adverse effects , Immunoconjugates/therapeutic use , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/immunology , Receptor, ErbB-3/antagonists & inhibitors , Receptor, ErbB-3/immunology , Young Adult , Maximum Tolerated Dose , Adolescent , Neoplasm Metastasis , China , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use
11.
MedComm (2020) ; 5(6): e588, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38868330

ABSTRACT

To identify the mechanism underlying macrosteatosis (MaS)-related graft failure (GF) in liver transplantation (LT) by multi-omics network analysis. The transcriptome and metabolome were assayed in graft and recipient plasma in discovery (n = 68) and validation (n = 89) cohorts. Differentially expressed molecules were identified by MaS and GF status. Transcriptional regulatory networks were generated to explore the mechanism for MaS-related inferior post-transplant prognosis. The differentially expressed molecules associated with MaS and GF were enriched in ferroptosis and peroxisome-related pathways. Core features of MaS-related GF were presented on decreased transferrin and impaired anti-oxidative capacity dependent upon dysregulation of transcription factors hepatocyte nuclear factor 4A (HNF4A) and hypoxia-inducible factor 1A (HIF1A). Furthermore, miR-362-3p and miR-299-5p inhibited transferrin and HIF1A expression, respectively. Lower M2 macrophages but higher memory CD4 T cells were observed in MaS-related GF cases. These results were validated in clinical specimens and cellular models. Systemic analysis of multi-omics data depicted a panorama of biological pathways deregulated in MaS-related GF. Transcriptional regulatory networks centered on transferrin and anti-oxidant responses were associated with poor MaS graft quality, qualifying as potential targets to improve prognosis of patients after LT.

12.
BMC Cardiovasc Disord ; 24(1): 315, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38909188

ABSTRACT

INTRODUCTION: Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc. CASE PRESENTATION: An aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent. CONCLUSIONS: This report may provide new management ideas for the interventional treatment of PV occlusion.


Subject(s)
Pulmonary Veins , Stents , Humans , Treatment Outcome , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/physiopathology , Pulmonary Veins/surgery , Chronic Disease , Pulmonary Veno-Occlusive Disease/therapy , Pulmonary Veno-Occlusive Disease/diagnostic imaging , Pulmonary Veno-Occlusive Disease/physiopathology , Pulmonary Veno-Occlusive Disease/etiology , Stenosis, Pulmonary Vein/diagnostic imaging , Stenosis, Pulmonary Vein/therapy , Stenosis, Pulmonary Vein/physiopathology , Stenosis, Pulmonary Vein/etiology , Mediastinitis/diagnosis , Mediastinitis/therapy , Male , Phlebography , Angioplasty, Balloon/instrumentation , Aged , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/diagnostic imaging , Fibrosis , Collateral Circulation , Pulmonary Circulation , Female
13.
Biomaterials ; 310: 122635, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38810386

ABSTRACT

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Photoacoustic Techniques , gamma-Glutamyltransferase , gamma-Glutamyltransferase/metabolism , Animals , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Photoacoustic Techniques/methods , Liver Neoplasms/diagnostic imaging , Liver Diseases/diagnostic imaging , Optical Imaging/methods , Mice , Male , Mice, Inbred BALB C , Liver/pathology , Liver/diagnostic imaging , Liver/enzymology , Fluorescent Dyes/chemistry
14.
Int J Surg ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38768472

ABSTRACT

BACKGROUND: Associating liver partition with portal vein ligation for staged liver resection (ALPPS) has been used in the treatment of patients with advanced or massive liver cancer without sufficient future liver remnant, but concerns remain regarding tumor outcomes and surgical safety. This study aims to evaluate the efficacy and safety of a new procedure, Hepatic artery restriction operation combined with ALPPS (HARO-ALPPS), in the treatment of HCC patients especially with severe fibrosis. METHODS: This retrospective study analyzed 8 patients who underwent HARO-ALPPS for HCC and compared their outcomes with 64 patients who underwent conventional ALPPS. The primary outcomes assessed were liver regeneration ability (measured by relative and absolute kinetic growth rates), postoperative complications, and mortality. The secondary outcomes included overall survival and disease-free survival. RESULTS: HARO-ALPPS significantly restricted the blood supply of the hepatic artery. One week after surgery, the blood flow of the right hepatic artery dropped to 62.1%. At the same time, HARO-ALPPS shows superior liver regeneration ability, which is particularly prominent in the background of liver fibrosis. No serious complications occurred after HARO-ALPPS. The overall survival rate of HARO-ALPPS was 75%, which was higher than that of ALPPS (64%, P=0.816). CONCLUSION: Compared to conventional ALPPS, HARO-ALPPS exhibits a better liver regeneration ability, and favorable long-term outcomes. Further prospective studies are needed to validate these findings and evaluate the long-term oncologic outcomes of this novel procedure.

15.
Materials (Basel) ; 17(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38793285

ABSTRACT

Single-pass-welding thermal cycles with different peak temperatures (Tp) were reproduced by a Gleeble 3800 to simulate the heat-affected zone (HAZ) of a Fe-24Mn-4Cr-0.4C-0.3Cu (wt.%) high manganese austenitic steel. Then, the effect of Tp on the microstructure and mechanical properties of the HAZ were investigated. The results indicate that recrystallization and grain growth play dominant roles. Based on this, the HAZ is proposed to categorize into three zones: the recrystallization heat-affected zone (RHAZ) with a Tp of 700~900 °C, the transition heat-affected zone (THAZ) with a Tp of 900~1000 °C, and the coarse grain heat-affected zone (CGHAZ) with a Tp of 1000~1300 °C. The recrystallization fraction was 29~44% in the RHAZ, rapidly increased to 87% in the THAZ, and exceeded 95% in the CGHAZ. The average grain size was 17~19 µm in the RHAZ, slightly increased to 22 µm in the THAZ, and ultimately increased to 37 µm in the CGHAZ. The yield strength in the RHAZ and THAZ was consistent with the change in recrystallization fraction, while in the CGHAZ, it satisfied the Hall-Petch relationship with grain size. In addition, compared with the base material, the Charpy impact absorbed energy at -196 °C decreased by 22% in the RHAZ, but slightly increased in the CGHAZ. This indicates that the theory of fine grain strengthening and toughening is not entirely applicable to the HAZ of the investigated high-Mn steel.

16.
EClinicalMedicine ; 72: 102622, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38745965

ABSTRACT

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

17.
Talanta ; 275: 126167, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710128

ABSTRACT

The expression of metabotropic glutamate receptor 5 (mGluR5) is subject to developmental regulation and undergoes significant changes in neuropsychiatric disorders and diseases. Visualizing mGluR5 by fluorescence imaging is a highly desired innovative technology for biomedical applications. Nevertheless, there are substantial problems with the chemical probes that are presently accessible. In this study, we have successfully developed a two-photon fluorogenic probe, mGlu-5-TP, based on the structure of mGluR5 antagonist 6-methyl-2-(phenylethynyl)pyridine (MPEP). Due to this antagonist-based probe selectively recognizes mGluR5, high expression of mGluR5 on living SH-SY5Y human neuroblastoma cells has been detected during intracellular inflammation triggered by lipopolysaccharides (LPS). Of particular significance, the probe can be employed along with two-photon fluorescence microscopy to enable real-time visualization of the mGluR5 in Aß fiber-treated neuronal cells, thereby establishing a connection to the progression of Alzheimer's disease (AD). These results revealed that the probe can be a valuable imaging tool for studying mGluR5-related diseases in the nervous system.


Subject(s)
Fluorescent Dyes , Neurons , Pyridines , Receptor, Metabotropic Glutamate 5 , Receptor, Metabotropic Glutamate 5/metabolism , Receptor, Metabotropic Glutamate 5/antagonists & inhibitors , Humans , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Neurons/metabolism , Pyridines/chemistry , Pyridines/pharmacology , Cell Line, Tumor , Lipopolysaccharides/pharmacology , Photons , Optical Imaging , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/analysis
18.
PLoS One ; 19(5): e0302641, 2024.
Article in English | MEDLINE | ID: mdl-38753596

ABSTRACT

The development of automated tools using advanced technologies like deep learning holds great promise for improving the accuracy of lung nodule classification in computed tomography (CT) imaging, ultimately reducing lung cancer mortality rates. However, lung nodules can be difficult to detect and classify, from CT images since different imaging modalities may provide varying levels of detail and clarity. Besides, the existing convolutional neural network may struggle to detect nodules that are small or located in difficult-to-detect regions of the lung. Therefore, the attention pyramid pooling network (APPN) is proposed to identify and classify lung nodules. First, a strong feature extractor, named vgg16, is used to obtain features from CT images. Then, the attention primary pyramid module is proposed by combining the attention mechanism and pyramid pooling module, which allows for the fusion of features at different scales and focuses on the most important features for nodule classification. Finally, we use the gated spatial memory technique to decode the general features, which is able to extract more accurate features for classifying lung nodules. The experimental results on the LIDC-IDRI dataset show that the APPN can achieve highly accurate and effective for classifying lung nodules, with sensitivity of 87.59%, specificity of 90.46%, accuracy of 88.47%, positive predictive value of 95.41%, negative predictive value of 76.29% and area under receiver operating characteristic curve of 0.914.


Subject(s)
Lung Neoplasms , Neural Networks, Computer , Tomography, X-Ray Computed , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/diagnosis , Tomography, X-Ray Computed/methods , Deep Learning , Solitary Pulmonary Nodule/diagnostic imaging , Solitary Pulmonary Nodule/diagnosis , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/diagnosis , Algorithms , Lung/diagnostic imaging , Lung/pathology , Radiographic Image Interpretation, Computer-Assisted/methods
19.
Mar Genomics ; 75: 101108, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735675

ABSTRACT

Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle.


Subject(s)
Genome, Bacterial , Sulfonium Compounds , Sulfur , Sulfonium Compounds/metabolism , Sulfur/metabolism , Seawater/microbiology , Sulfides/metabolism , China
20.
Talanta ; 275: 126151, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38678927

ABSTRACT

This article discusses the importance of early tumor detection, particularly in liver cancer, and the role of leucine aminopeptidase (LAP) as a potential marker for liver cancer diagnosis and prognosis assessment. The article highlights the limitations of current tumor markers and the need for new markers and multi-marker approaches to improve accuracy. The authors introduce a novel near-infrared fluorescent probe, NTAP, designed for LAP detection. They describe the synthesis of the probe and evaluate its spectral properties, including the LOD was 0.0038 U/mL, and QY was 0.32 %. The kinetic properties of NTAP, such as the relationship between LAP concentration (0-0.08 U/mL), reaction time (3 min), and fluorescence excitation spectra (475 nm) and emission spectra (715 nm) are investigated. The article also discusses the stability and selectivity of the probe and its ability to detect LAP in complex samples. Cellular imaging experiments demonstrate the NATP specificity and selectivity in detecting LAP activity and its inhibition. Animal models of liver and lung metastasis are used to evaluate the probe's imaging capabilities, showing its ability to accurately locate and detect metastatic lesions. The article concludes by emphasizing the potential applications of the NTAP probe in early tumor diagnosis, treatment monitoring, and the study of tumor metastasis mechanisms.


Subject(s)
Fluorescent Dyes , Leucyl Aminopeptidase , Neoplasm Metastasis , Animals , Humans , Mice , Disease Progression , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Infrared Rays , Leucyl Aminopeptidase/metabolism , Leucyl Aminopeptidase/analysis , Liver Neoplasms/diagnostic imaging , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Optical Imaging
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