ABSTRACT
The demand for a high-performance position sensitive detector (PSD), a novel type of photoelectric sensor, is increasing due to advancements in digitization and automation technology. Cadmium sulfide (CdS), a non-centrosymmetric material, holds significant potential in photoelectric devices. However, the pyroelectric effect of CdS in PSDs and its influence on lateral photoresponse are still unknown. In this work, we fabricated an ITO/CdS/Si heterojunction using chemical bath deposition (CBD) and investigated the pyro-phototronic effect under nonuniform illumination. The theory of electron-hole pairs' generation, separation, and carrier diffusion was carefully considered to understand the underlying mechanisms. Our experimental findings revealed that the device exhibited an exceptionally high position sensitivity (PS) of 1061.3 mV/mm, surpassing the generally observed PS of 655.1 mV/mm induced by single photovoltaic effect by 160.5%. Meanwhile, the PSD demonstrated rapid response times of 0.01 and 0.04 ms, respectively. Moreover, the influence of ambient temperature and electrode distance on the pyro-phototronic effect was well analyzed. Notably, the PSD exhibited remarkable stability even at ambient temperatures up to 150 °C. Despite the considerable working distance of 11 mm, the PS of the PSD remained at 128.99 mV/mm. These findings provide valuable theoretical and experimental foundations for optimizing the design and implementation of high-performance large working distance PSDs.
ABSTRACT
Acesulfame (ACE), sucralose (SUC), cyclamate (CYC), and saccharin (SAC) are widely used artificial sweeteners that undergo negligible metabolism in the human body, and thus ubiquitously exist in wastewater treatment plants (WWTPs). Due to their persistence in WWTPs, ACE and SUC are found in natural waters globally. Wastewater samples were collected from the primary influent, primary effluent, secondary effluent, and final effluent of a WWTP in Alberta, Canada between August 2022 and February 2023, and the artificial sweeteners concentrations were measured by LC-MS/MS. Using wastewater-based epidemiology, the daily per capita consumption of ACE in the studied wastewater treatment plant catchment was estimated to be the highest in the world. Similar to other studies, the removal efficiency in WWTP was high for SAC and CYC, but low or even negative for SUC. However, ACE removal remained surprisingly high (>96%), even in the cold Canadian winter months. This result may indicate a further adaptation of microorganisms capable of biodegrading ACE in WWTP. The estimated per capita discharge into the environment of ACE, CYC, and SAC is low in Alberta due to the prevalent utilization of secondary treatment throughout the province, but is 17.4-18.8 times higher in Canada, since only 70.3% of total discharged wastewater in Canada undergoes secondary treatment.
Subject(s)
Sucrose/analogs & derivatives , Sweetening Agents , Thiazines , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical , Wastewater/chemistry , Sweetening Agents/analysis , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/metabolism , Alberta , Thiazines/analysis , Saccharin/analysis , Environmental Monitoring , Biodegradation, Environmental , Tandem Mass Spectrometry , Sucrose/analysis , Sucrose/metabolismABSTRACT
OBJECTIVE: This study aims to investigate the influence of delirium following radical prostatectomy on cognitive function and health perception during the recovery period. METHODS: Data were collected from patients who underwent radical prostatectomy at our institution between May 2020 and May 2022. Postoperative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), categorising patients into delirium and non-delirium groups. The Montreal Cognitive Assessment (MoCA) and the Brief Illness Perception Questionnaire (BIPQ) were employed to evaluate patients' mental health pre-and post-surgery. Comparative analyses were conducted between patients with and without delirium in the critical care unit, and correlation analyses were performed. RESULTS: The study revealed a delirium incidence rate of 19.13%. Patients in the delirium group exhibited significantly higher age and ICU length of stay compared to those without delirium (p < 0.05). No significant differences were observed in MoCA scores one day before surgery and seven days after surgery, as well as BIPQ scores one day before surgery, five days after surgery and seven days after surgery between the delirium and non-delirium groups (p > 0.05); However, the MoCA scores in the delirium group were significantly lower than those of the non-delirium group on the second and fifth days post-surgery. Additionally, the BIPQ scores in the delirium group were significantly higher than those in the non-delirium group two days after surgery (p < 0.001). A moderate negative correlation was observed between MoCA scores and CAM-ICU scores, and a moderate positive correlation was identified between BIPQ scores and CAM-ICU scores (p < 0.001). CONCLUSIONS: Patients experiencing delirium after radical prostatectomy are at a higher risk of cognitive function impairment and disease threat perception. A significant correlation exists between postoperative delirium and cognitive function as well as health perception.
Subject(s)
Delirium , Emergence Delirium , Male , Humans , Delirium/epidemiology , Delirium/etiology , Delirium/psychology , Emergence Delirium/complications , Cognition , Prostatectomy/adverse effects , PerceptionABSTRACT
An electron transport layer (ETL) with a suitable gradient energy level can enhance electron transfer, suppress carrier recombination, and effectively improve the photoresponse of photodetectors (PDs). In this letter, a series of ITO/ZnO/CdS/MAPbI3/Spiro-OMeTAD heterojunction PDs were prepared by incorporating a ZnO layer at the CdS/ITO interface upon varying the thickness from 0 to 95 nm. The optimized band arrangement in the PD results in an excellent self-powering ability and improved photoresponse. Moreover, both the photovoltaic and pyroelectric responses strongly correlate with the thickness of the ZnO layer. The PD with an optimal ZnO thin film thickness of 50 nm achieves a huge responsivity (R) of 1.19 × 104 V/W and detectivity (D) of 2.22 × 109 Jones, primarily due to the strengthened pyro-phototronic effects enabled by the dual ETL layers. In addition, the enhanced pyroelectric effect broadens the spectral range of the PD to 360-1550 nm, largely surpassing the band gap of the heterojunction.
ABSTRACT
Mutations in isocitrate dehydrogenases (IDH) are oncogenic events due to the generation of oncogenic metabolite 2-hydroxyglutarate. However, the role of wild-type IDH in cancer development remains elusive. Here we show that wild-type IDH2 is highly expressed in triple negative breast cancer (TNBC) cells and promotes their proliferation in vitro and tumor growth in vivo. Genetic silencing or pharmacological inhibition of wt-IDH2 causes a significant increase in α-ketoglutarate (α-KG), indicating a suppression of reductive tricarboxylic acid (TCA) cycle. The aberrant accumulation of α-KG due to IDH2 abrogation inhibits mitochondrial ATP synthesis and promotes HIF-1α degradation, leading to suppression of glycolysis. Such metabolic double-hit results in ATP depletion and suppression of tumor growth, and renders TNBC cells more sensitive to doxorubicin treatment. Our study reveals a metabolic property of TNBC cells with active utilization of glutamine via reductive TCA metabolism, and suggests that wild-type IDH2 plays an important role in this metabolic process and could be a potential therapeutic target for TNBC.
Subject(s)
Cell Proliferation , Citric Acid Cycle , Isocitrate Dehydrogenase , Ketoglutaric Acids , Triple Negative Breast Neoplasms , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/metabolism , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Humans , Female , Animals , Cell Line, Tumor , Citric Acid Cycle/drug effects , Ketoglutaric Acids/metabolism , Mice , Cell Proliferation/drug effects , Glycolysis/drug effects , Adenosine Triphosphate/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mitochondria/metabolism , Mitochondria/drug effects , Glutamine/metabolism , Xenograft Model Antitumor Assays , MutationABSTRACT
Metabolic changes play a crucial role in determining the status and function of macrophages, but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood. Here, we investigated the phenotype, contribution, and regulatory mechanisms of lipid droplet (LD)-laden macrophages (LLMs) in hepatocellular carcinoma (HCC). Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients. The LLMs displayed immunosuppressive phenotypes (with extensive expression of TREM2, PD-L1, CD206, and CD163) and attenuated the antitumor activities of CD8+ T cells. Mechanistically, tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages. LDs prolong LLM survival and promote CCL20 secretion, which further recruits CCR6+ Tregs to HCC tissue. Inhibiting LLM formation by targeting DGAT1 and DGAT2, which catalyze the synthesis of triglycerides, significantly reduced Treg recruitment, and delayed tumor growth in a mouse hepatic tumor model. Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.
ABSTRACT
The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1+ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , B7-H1 Antigen/metabolism , Neutrophils/metabolism , Serum Amyloid A Protein/metabolism , Programmed Cell Death 1 Receptor , GlycolysisABSTRACT
Metabolism in host cells can be modulated after viral infection, favoring viral survival or clearance. Here, we report that lipid droplet (LD) synthesis in host cells can be modulated by yin yang 1 (YY1) after porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in active antiviral activity. As a ubiquitously distributed transcription factor, there was increased expression of YY1 upon PRRSV infection both in vitro and in vivo. YY1 silencing promoted the replication of PRRSV, whereas YY1 overexpression inhibited PRRSV replication. PRRSV infection led to a marked increase in LDs, while YY1 knockout inhibited LD synthesis, and YY1 overexpression enhanced LD accumulation, indicating that YY1 reprograms PRRSV infection-induced intracellular LD synthesis. We also showed that the viral components do not colocalize with LDs during PRRSV infection, and the effect of exogenously induced LD synthesis on PRRSV replication is nearly lethal. Moreover, we demonstrated that YY1 affects the synthesis of LDs by regulating the expression of lipid metabolism genes. YY1 negatively regulates the expression of fatty acid synthase (FASN) to weaken the fatty acid synthesis pathway and positively regulates the expression of peroxisome proliferator-activated receptor gamma (PPARγ) to promote the synthesis of LDs, thus inhibiting PRRSV replication. These novel findings indicate that YY1 plays a crucial role in regulating PRRSV replication by reprogramming LD synthesis. Therefore, our study provides a novel mechanism of host resistance to PRRSV and suggests potential new antiviral strategies against PRRSV infection.IMPORTANCEPorcine reproductive and respiratory virus (PRRSV) has caused incalculable economic damage to the global pig industry since it was first discovered in the 1980s. However, conventional vaccines do not provide satisfactory protection. It is well known that viruses are parasitic pathogens, and the completion of their replication life cycle is highly dependent on host cells. A better understanding of host resistance to PRRSV infection is essential for developing safe and effective strategies to control PRRSV. Here, we report a crucial host antiviral molecule, yin yang 1 (YY1), which is induced to be expressed upon PRRSV infection and subsequently inhibits virus replication by reprogramming lipid droplet (LD) synthesis through transcriptional regulation. Our work provides a novel antiviral mechanism against PRRSV infection and suggests that targeting YY1 could be a new strategy for controlling PRRSV.