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1.
Nano Lett ; 24(38): 11921-11928, 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39268850

ABSTRACT

Advanced photodetectors are crucial for high-fidelity optical communication. However, the tradeoff between high external quantum efficiency (EQE) and high light fidelity (Li-Fi) frequency often limits data transmission accuracy and timeliness. Here, we report a photodetector consisting of lead sulfide (PbS) colloidal quantum dots (CQDs) with near-infrared responsiveness and perovskite frameworks responsible for the charge transport to overcome the EQE × Li-Fi constraint. Optimizing the PbS CQDs distribution and trap depth in the perovskite layer enhances charge injection, achieving a device gain of 11892% for 1200 nm photons and a response frequency of 24 kHz at -2 V. The device exhibits a record EQE × Li-Fi frequency product of 106 Hz. We have applied the detector to near-infrared optical communications at a data transfer rate of 2000 bits per second (2 kbps) to demonstrate the advances in high fidelity, the device retains over 98% of the original waveform information in its output.

2.
Adv Healthc Mater ; : e2401950, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39276002

ABSTRACT

Poor in vivo characteristics of gambogic acid (GA) and difficulties in industrial manufacturing of its nanocarriers have hindered its clinical translation. Therefore, a reproducible nano-drug delivery system must be developed to realize simpler manufacture and address inherent defects of GA, such as short circulation and severe side effects, in order to facilitate its clinical application. Herein, a drug self-assembled nanoparticles (NPs) consisting of a hydrophobic prodrug based on GA and oleyl alcohol (OA), as well as vitamin E-polyethylene glycol succinate (TPGS) as a shield to improve the stability of the NPs is reported. The preparation method is simple enough to stably facilitate large-scale manufacturing. The self-assembled NPs exhibit a remarkably high drug-loading capacity, and their prolonged circulation enables the NPs to demonstrate superior antitumor efficacy in both cellular and animal models. The flexible hydrophobic long chain wraps GA groups, which mitigates vascular irritation and reduces hemolysis rates. Consequently, the prodrug nano-system addresses GA-related concerns regarding stability, efficacy, and safety, offering a simple, stable, and secure nano-platform for similar candidate drugs.

3.
Br J Ophthalmol ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227133

ABSTRACT

BACKGROUND: To assess predictive value of short-term choroidal changes for future myopic shift in children. METHODS: 577 eyes of 289 primary school children were prospectively followed for 2 years. Cycloplegic refractions at baseline, 1 year and 2 years, and choroidal measurements by optical coherence tomography at baseline and 3 months, were used for analyses. Myopic shift was defined as refraction change of at least -0.50 dioptre/year, at 2 years compared with baseline. RESULTS: 228 participants (455 eyes) completed 2-year follow-up. Approximately 37.6% of 311 initially non-myopic eyes and 73.6% of 144 initially myopic eyes developed a myopic shift. Notably, at 3 months greater reductions were found in initially myopic eyes with myopic shift, than in those without myopic shift-in choroidal thickness (ChT), luminal area (LA), stromal area (SA) and total choroidal area (TCA), but no significant differences in any choroidal parameters were observed between non-myopic eyes, with and without myopic shift. Multivariable analyses showed that in myopic eyes, each percentage increase in ChT, LA, SA and TCA was associated with reduced odds of myopic shift (all p<0.001). Similar associations were observed in non-myopic eyes, with smaller effects than in myopic eyes. Adding a 3-month percentage change of each choroidal parameter to a basic model including age, gender, parental myopia and baseline refraction significantly improved the predictive performance in myopic eyes (area under the receiver operating characteristic curves increasing from 0.650 to approximately 0.800, all p<0.05), but not in non-myopic eyes. CONCLUSION: Short-term choroidal changes could act as early indicators for future myopic shift in children.

4.
Adv Healthc Mater ; : e2401537, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39205549

ABSTRACT

Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-ß (TGF-ß) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-ß at tumor-resection sites, whose unique mechanism for local TGF-ß amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-ß. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-ß and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.

5.
NPJ Parkinsons Dis ; 10(1): 142, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095359

ABSTRACT

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson's disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep-wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2-10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

6.
Front Genet ; 15: 1404515, 2024.
Article in English | MEDLINE | ID: mdl-39144722

ABSTRACT

Background: Breast cancer recurrence and lymph node metastasis significantly impact patient outcomes. Understanding the molecular mechanisms behind these processes is crucial for developing effective treatments. CCN5 and E-cadherin are proteins involved in cell adhesion and epithelial-mesenchymal transition (EMT), playing roles in breast cancer progression. Objective: This study aimed to analyze the expression levels and clinical significance of CCN5 and E-cadherin in primary and recurrent breast cancer lesions. Methods: Immunohistochemical staining using the SP method was performed to detect CCN5 and E-cadherin expression levels in 28 normal breast tissue samples, 52 primary breast cancer lesions, and paired recurrent chest wall lesions. The expression levels of these proteins were compared across different tissue types and correlated with lymph node metastasis. Results: CCN5 and E-cadherin expression levels significantly differed among normal breast tissues, primary breast cancer lesions, and recurrent lesions (Χ2 = 18.934 and Χ2 = 14.516, p < 0.05). Primary breast cancer lesions exhibited higher CCN5 and E-cadherin expression levels compared with recurrent lesions and normal tissues, although these differences were not statistically significant. Patients without lymph node metastases exhibited significantly higher expression levels of CCN5 and E-cadherin compared with those with lymph node metastases (Χ2 = 9.775, Χ2 = 9.1479, p < 0.05). A positive correlation between CCN5 and E-cadherin expression levels was found in breast cancer tissues (r = 0.398, p < 0.001). Conclusion: CCN5 and E-cadherin were expressed at lower levels in recurrent breast cancer tissues and those with lymph node metastases, indicating their potential roles in breast cancer recurrence and metastasis. These findings suggest that CCN5 and E-cadherin might work synergistically to influence breast cancer progression.

7.
Small ; : e2404696, 2024 Aug 18.
Article in English | MEDLINE | ID: mdl-39155427

ABSTRACT

Graphitic carbon nitride (g-C3N4) is a prominent photocatalyst that has attracted substantial interest in the field of photocatalytic environmental remediation due to the low cost of fabrication, robust chemical structure, adaptable and tunable energy bandgaps, superior photoelectrochemical properties, cost-effective feedstocks, and distinctive framework. Nonetheless, the practical application of bulk g-C3N4 in the photocatalysis field is limited by the fast recombination of photogenerated e--h+ pairs, insufficient surface-active sites, and restricted redox capacity. Consequently, a great deal of research has been devoted to solving these scientific challenges for large-scale applications. This review concisely presents the latest advancements in g-C3N4-based photocatalyst modification strategies, and offers a comprehensive analysis of the benefits and preparation techniques for each strategy. It aims to articulate the complex relationship between theory, microstructure, and activities of g-C3N4-based photocatalysts for atmospheric protection. Finally, both the challenges and opportunities for the development of g-C3N4-based photocatalysts are highlighted. It is highly believed that this special review will provide new insight into the synthesis, modification, and broadening of g-C3N4-based photocatalysts for atmospheric protection.

8.
Neurosci Biobehav Rev ; 164: 105810, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39009293

ABSTRACT

Sleep disturbances, encompassing altered sleep physiology or disorders like insomnia and sleep apnea, profoundly impact physiological functions and elevate disease risk. Despite extensive research, the underlying mechanisms and sex-specific differences in sleep disorders remain elusive. While polysomnography serves as a cornerstone for human sleep studies, animal models provide invaluable insights into sleep mechanisms. However, the availability of animal models of sleep disorders is limited, with each model often representing a specific sleep issue or mechanism. Therefore, selecting appropriate animal models for sleep research is critical. Given the significant sex differences in sleep patterns and disorders, incorporating both male and female subjects in studies is essential for uncovering sex-specific mechanisms with clinical relevance. This review provides a comprehensive overview of various rodent models of sleep disturbance, including sleep deprivation, sleep fragmentation, and circadian rhythm dysfunction. We evaluate the advantages and disadvantages of each model and discuss sex differences in sleep and sleep disorders, along with potential mechanisms. We aim to advance our understanding of sleep disorders and facilitate sex-specific interventions.


Subject(s)
Disease Models, Animal , Sex Characteristics , Sleep Wake Disorders , Animals , Sleep Wake Disorders/physiopathology , Rodentia , Humans , Sleep Deprivation/physiopathology , Female , Male
9.
Sensors (Basel) ; 24(14)2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39065874

ABSTRACT

Synthetic Aperture Radar (SAR) is renowned for its all-weather and all-time imaging capabilities, making it invaluable for ship target recognition. Despite the advancements in deep learning models, the efficiency of Convolutional Neural Networks (CNNs) in the frequency domain is often constrained by memory limitations and the stringent real-time requirements of embedded systems. To surmount these obstacles, we introduce the Split_ Composite method, an innovative convolution acceleration technique grounded in Fast Fourier Transform (FFT). This method employs input block decomposition and a composite zero-padding approach to streamline memory bandwidth and computational complexity via optimized frequency-domain convolution and image reconstruction. By capitalizing on FFT's inherent periodicity to augment frequency resolution, Split_ Composite facilitates weight sharing, curtailing both memory access and computational demands. Our experiments, conducted using the OpenSARShip-4 dataset, confirm that the Split_ Composite method upholds high recognition precision while markedly enhancing inference velocity, especially in the realm of large-scale data processing, thereby exhibiting exceptional scalability and efficiency. When juxtaposed with state-of-the-art convolution optimization technologies such as Winograd and TensorRT, Split_ Composite has demonstrated a significant lead in inference speed without compromising the precision of recognition.

10.
Molecules ; 29(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38930930

ABSTRACT

Considering that heavy-metal contamination of seawater is getting worse, building a quick, accurate and portable device for detecting trace zinc in seawater in real time would be very beneficial. In this work, a microfluidic system was developed that includes a planar disc electrode, a micro-cavity for detection, an electrochemical workstation, a computer, a container for waste liquid reprocessing, an external pipeline and other components as well as a graphene/cerium oxide/nano-cerium oxide/Nafion composite membrane was used to modify the planar disc electrode (GR/CeO2/Nafion/Au) to investigate the electrochemical behaviour of Zn(II) using cyclic voltammetry, square-wave voltammetry and orthogonal test methods. Under optimal experimental conditions, the peak reaction current of Zn(II) showed a good linear relationship with the concentration of Zn(II) in the range of 1-900 µg/L with a correlation coefficient of 0.998, and the detection limit of the method was 0.87 µg/L. In addition, the microfluidic system had good stability, reproducibility and anti-interference. The system was used for determining zinc ions in real seawater samples, and the results were very similar to those of inductively coupled plasma-emission spectrometry, demonstrating the practicality of the system for the detection of trace zinc.

11.
Med Phys ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843522

ABSTRACT

BACKGROUND: Cirrhosis patients often exhibit clinical symptoms such as right liver atrophy, portal hypertension, spleen enlargement and increased blood supply, which exhibit considerable variation between the left and right liver sections. These differences are hypothesized to stem from disparities in blood flow within the left and right portal vein (PV) branches. However, rigorous quantitative evidence remains scarce. PURPOSE: We mainly aim at quantitatively revealing the relationship between the blood flow rates of two PV branches and liver volumes, and providing quantitative evidence and theoretical support for the diagnosis and treatment of cirrhosis from the perspective of hemodynamics. METHODS: Five cirrhotic patients and two healthy volunteers from Beijing Friendship Hospital are investigated. Their PV blood flow models are established based on computed tomography (CT) images and finite volume simulations. The volume of the left and right liver lobes are measured in 3-matic. The distributions of blood source in the PV branches are tracked by streamline analysis. The blood flow rates are quantitatively counted by integrating the blood source velocities. Linear analysis is performed to build the relationship between liver volumes and PV blood flow distributions. RESULTS: Streamline analysis reveals significant differences in blood distribution between the left and right PV branches. The majority of blood from the superior mesenteric vein (SMV) flowed into the right portal vein (RPV), while most blood from the splenic vein (SV) entered the left portal vein (LPV). The main PV pressure drop linearly increases with the SV blood velocity for all PV structures of patients and healthy volunteers. The flow rate ratio QRPV/QLPV demonstrates an increase in tandem with the volume ratio VR/VL, exhibiting a linear correlation with the Pearson correlation coefficient being 0.93. CONCLUSION: The differences in the blood distributions are consistent with the clinicians' knowledge and validate our simulations. We demonstrated a linear increase in PV pressure with elevated SV blood velocity. Additionally, the volumes of the left and right hepatic lobes exhibited a positive correlation with blood flow rates in the corresponding PV branches.

13.
ACS Omega ; 9(22): 23843-23852, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38854572

ABSTRACT

The stability of both the structure and activity of MoS2 nanocatalysts is crucial for minimizing the catalyst cost of the slurry-phase (SP) catalytic hydrogenation. MoS2-GP and MoS2-SP catalysts were, respectively, obtained by gas-phase (denoted as GP) and SP aging of fresh MoS2 catalysts. The MoS2-SP catalyst demonstrated a comparable catalytic hydrogenation activity to that of the fresh MoS2 catalyst, which is about 1.7 times of that for the MoS2-GP catalyst. After 12 cycles of the MoS2-SP catalyst, the obtained Cy12 catalyst demonstrates a retention of 92.0% of its initial catalytic activity. The MoS2-SP catalyst exhibits an impressive stability of catalytic hydrogenation. The MoS2-SP catalyst exhibits average stacking layers of 3.3 and an average slab of 5.2 nm and exposes 14.0% of active sites. The MoS2-SP catalyst can serve as a highly active and stable catalyst for catalytic hydrogenation. This finding can offer valuable insights into the stability of the hydrogenation catalyst in SP hydrogenation technology.

14.
Nano Lett ; 24(25): 7593-7600, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38869928

ABSTRACT

In traditional optical wireless communication (OWC) systems, the simultaneous use of multiple sets of light-emitting diodes (LEDs) and photodetectors (PDs) increases the system complexity and instability. Here we report bifunctional light-emitting photodetectors (LEPDs) fabricated with quasi-2D perovskite (F-PEA)2Cs4Pb5I11Br5 as light-emitting/detecting layers for efficient, miniaturized, and intelligent bidirectional OWC. By simply changing the solvent composition of the precursor solution and using antisolvent engineering, we manipulated the crystal orientation and phase distribution of (F-PEA)2Cs4Pb5I11Br5, realizing high irradiance (4.36 µW cm-2) and a -3 dB refresh rate (0.21 MHz) of electroluminescence in LED mode as well as low noise (below 1 pA Hz-1/2) and high responsivity (0.1 A W-1) in PD mode. The rapid and accurate OWC process was demonstrated through interaction of LEPDs. We also demonstrated the high-fidelity compression and digitization of high-resolution (256 × 256 pixels) color images using the four-step phase shift method to realize intelligent encrypted image OWC.

15.
Int J Biol Macromol ; 275(Pt 2): 133328, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945702

ABSTRACT

Alginate (Alg) as co-extruded casing is of interest to the meat industry as replacers for natural sausage casing. However, these studies on the mechanical reinforcement of Alg-based film are still limited in the wet state (e.g. co-extrusion process). In this work, Alg-D with the highest viscosity-average molecular weight (1.12 × 105) was selected from four types of alginates based on the results of the viscosity of Alg solutions and film strength. Next, three celluloses (cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and microfibrillated fiber (MFC)) were added to the Alg-D matrix at different concentrations. SEM showed that the cross section of the Alg-based films became more compact and uniform when the size of celluloses decreased. The tensile test revealed that the strength (TS) of Alg-based films exhibited an initial increase followed by a subsequent drop as the cellulose content rose. The best mechanical strengthening effect was the Alg-CNC film (1.16 MPa), which increased by 93.33 % compared with that of pure Alg. Cooking treatment could further enhance this trend. The opacity increased gradually with the increase of cellulose content, while these films were still transparent enough for food packaging. These findings would have potential applications in food packaging, especially co-extruded sausage casings.


Subject(s)
Alginates , Cellulose , Cooking , Food Packaging , Tensile Strength , Alginates/chemistry , Cellulose/chemistry , Cooking/methods , Food Packaging/methods , Nanofibers/chemistry , Viscosity , Nanoparticles/chemistry
16.
Asian J Psychiatr ; 97: 104088, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38810490

ABSTRACT

INTRODUCTION: Suicide attempts (SA) are a significant contributor to suicide deaths, and non-suicidal self-injury (NSSI) can increase the risk of SA. Many adolescents experience both NSSI and SA, which are affected by various factors. This study aimed to identify the risk factors and essential warning signs of SA, establish a predictive model for SA using multiple dimensions and large samples, and provide a multidimensional perspective for clinical diagnosis and intervention. METHODS: A total of 9140 participants aged 12-18 years participated in an online survey; 6959 participants were included in the statistical analysis. A multilayer perceptron algorithm was used to establish a prediction model for adolescent SA (with or without); adolescents with NSSI behavior were extracted as a subgroup to establish a prediction model. RESULTS: Both the prediction model performance of the SA group and the NSSI-SA subgroup were strong, with high accuracy, and AUC values of 0.93 and 0.88, indicating good discrimination. Decision curve analysis (DCA) demonstrated that the clinical intervention value of the prediction results was high and that the clinical intervention benefits of the NSSI-SA subgroup were greater than those of the SA group. CONCLUSIONS: Our study demonstrated that the predictive model has a high degree of accuracy and discrimination, thereby identifying significant factors associated with adolescent SA. As long as adolescents exhibit NSSI behavior, relative suicide interventions should be implemented to prevent future hazards. This study can provide guidance and more nuanced insights for clinical diagnosis as well as a foundation for clinical treatment.


Subject(s)
Self-Injurious Behavior , Suicide, Attempted , Humans , Adolescent , Self-Injurious Behavior/epidemiology , Female , Suicide, Attempted/statistics & numerical data , Male , Child , China/epidemiology , Neural Networks, Computer , Adolescent Behavior , Risk Factors , East Asian People
17.
Science ; 384(6696): 670-676, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38723074

ABSTRACT

Electrochemistry offers a sustainable synthesis route to value-added fine chemicals but is often constrained by competing electron transfer between the electrode and redox-sensitive functionalities distinct from the target site. Here, we describe an ion-shielding heterogeneous photoelectrocatalysis strategy to impose mass-transfer limitations that invert the thermodynamically determined order of electron transfer. This strategy is showcased to enable decarboxylative trifluoromethylation of sensitive (hetero)arenes by using trifluoroacetate, an inexpensive yet relatively inert trifluoromethyl group (CF3) source. An ion-shielding layer, formed by trifluoroacetate anions electrostatically adsorbed on a positive molybdenum-doped tungsten trioxide (WO3) photoanode, prevents undesired electron transfer between substrates and photogenerated holes. The practicality of the developed method was demonstrated with robust photoanode stability (approximately 380 hours), a good substrate scope, and scaling capability to achieve 100-gram synthesis by using photoelectrochemical flow cells.

18.
Eur J Med Chem ; 272: 116463, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38704944

ABSTRACT

Butyrylcholinesterase (BChE) has attracted wide interest as a promising target in Alzheimer's disease (AD) investigation. BChE is considered to play a compensable role of hydrolyzing acetylcholine (ACh), and its positive correlation with ß-amyloid (Aß) deposition also promotes disease progression. Herein, we uncovered a selective potent BChE inhibitor S21-1011 (eqBChE IC50 = 0.059 ± 0.006 µM, hBChE IC50 = 0.162 ± 0.069 µM), which presented satisfactory druggability and therapeutic efficacy in AD models. In pharmacokinetics (PK) studies, S21-1011 showed excellent blood-brain barrier (BBB) permeability, metabolism stability and high oral-bioavailability. In pharmacodynamic (PD) studies, it protected neural cells from toxicity and inflammation stimulation in vitro. Besides, it also exerted anti-inflammatory effect and alleviated cognitive impairment in mice models induced by lipopolysaccharides (LPS) and Aß. Generally, this compound has been confirmed to function as a neuroprotector and cognition improver in various AD pathology-like models. Therefore, S21-1011, a novel potent BChE inhibitor, could be considered as a potential anti-AD candidate worthy of more profound investigation.


Subject(s)
Alzheimer Disease , Butyrylcholinesterase , Cholinesterase Inhibitors , Quinolines , Butyrylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/chemical synthesis , Mice , Humans , Structure-Activity Relationship , Quinolines/chemistry , Quinolines/pharmacology , Quinolines/chemical synthesis , Drug Discovery , Molecular Structure , Male , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Dose-Response Relationship, Drug , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/chemical synthesis , Piperazines/pharmacology , Piperazines/chemistry , Piperazines/chemical synthesis , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Inflammation/drug therapy , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects
19.
Am J Transplant ; 24(10): 1837-1856, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38642712

ABSTRACT

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.


Subject(s)
Carcinoma, Hepatocellular , Graft Rejection , Immune Checkpoint Inhibitors , Liver Neoplasms , Liver Transplantation , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Retrospective Studies , Male , Female , Liver Neoplasms/drug therapy , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Graft Rejection/etiology , Follow-Up Studies , Prognosis , Graft Survival/drug effects , Survival Rate , Risk Factors
20.
Cell Oncol (Dordr) ; 47(4): 1391-1403, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38607517

ABSTRACT

PURPOSE: GPX8, which is found in the endoplasmic reticulum lumen, is a member of the Glutathione Peroxidases (GPXs) family. Its role in hepatocellular carcinoma (HCC) is unknown. METHODS: Immunohistochemical staining was used to detect the protein levels of GPX8 in HCC tissue microarrays. A short hairpin RNA lentivirus was used to knock down GPX8, and the main signaling pathways were investigated using transcriptome sequencing and a phosphorylated kinase array. The sphere formation assays, cloning-formation assays and cell migration assays were used to evaluate the stemness and migration ability of HCC cells. Identifying the GPX8-interacting proteins was accomplished through immunoprecipitation and protein mass spectrometry. RESULTS: The GPX8 protein levels were downregulated in HCC patients. Low expression of GPX8 protein was related to early recurrence and poor prognosis in HCC patients. GPX8 knockdown could enhance the stemness and migration ability of HCC cells. Consistently, Based on transcriptome analysis, multiple signaling pathways that include the PI3K-AKT and signaling pathways that regulate the pluripotency of stem cells, were activated after GPX8 knockdown. The downregulation of GPX8 could increase the expression of the tumor stemness markers KLF4, OCT4, and CD133. The in vivo downregulation of GPX8 could also promote the subcutaneous tumor-forming and migration ability of HCC cells. MK-2206, which is a small-molecule inhibitor of AKT, could reverse the tumor-promoting effects both in vivo and in vitro. We discovered that GPX8 and the 71-kDa heat shock cognate protein (Hsc70) have a direct interaction. The phosphorylation of AKT encouraged the translocation of Hsc70 into the nucleus and the expression of the PI3K p110 subunit, thereby increasing the downregulation of GPX8. CONCLUSION: The findings from this study demonstrate the anticancer activity of GPX8 in HCC by inactivating the Hsc70/AKT pathway. The results suggest a possible therapeutic target for HCC.


Subject(s)
Carcinoma, Hepatocellular , Cell Movement , Down-Regulation , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Neoplastic Stem Cells , Signal Transduction , Animals , Female , Humans , Male , Mice , Middle Aged , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Movement/genetics , Down-Regulation/genetics , Glutathione Peroxidase/metabolism , Glutathione Peroxidase/genetics , Kruppel-Like Factor 4 , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Mice, Inbred BALB C , Mice, Nude , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/genetics
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