A perovskite solar cell-photothermal-thermoelectric tandem system for enhanced solar energy utilization.

Photovoltaic-thermoelectric (PV-TE) tandem system has been considered as an effective way to fully utilize the solar spectrum, and has been demonstrated in a perovskite solar cell (PSC)-thermoelectric (TE) configuration. However, the conventional PSC-TE tandem architecture cannot convert infrared light transmitted through the upper PSC into heat effectively, impeding the heat-electricity conversion of TE devices. Herein, a semi-transparent PSC-photothermal-TE tandem system is designed for improved photothermal utilization. Through optimizing the buffer layer of the back transparent electrode, semi-transparent PSC with a power conversion efficiency (PCE) of 13% and an average transmittance of 53% in the range of 800-1500 nm was obtained. On this basis, a photothermal thin film was introduced between the semi-transparent PSC and the TE device, which increased the efficiency contribution ratio of the TE device from 14% to 19%, showing enhanced utilization of AM 1.5 G solar spectrum and improved photo-thermal-electric conversion efficiency.

We have constructed a semi-transparent perovskite solar cell-photothermal-thermoelectric tandem system through the optimization of transparent back electrode and the introduction of photothermal thin-film, realizing enhanced utilization of solar energy.

Astaxanthin encapsulation in soybean protein isolate-sodium alginate complexes-stabilized nanoemulsions: antioxidant activities, environmental stability, and in vitro digestibility.

BACKGROUND: Nanoemulsions (NEs) have been considered an effective carrier to protect environmentally labile bioactive compounds from degradation during food processing. Among the numerous types of NEs, biopolymer-stabilized NEs have gained much attention to achieve this function because of the extensive sources, biocompatibility, and tunability. Therefore, the antioxidant activities, environmental stability, and in vitro digestibility of astaxanthin (AST)-loaded soybean protein isolate (SPI)-alginate (SA) complexes-stabilized NEs (AST-SPI-SA-NEs) were investigated in this study. RESULTS: The AST-SPI-SA-NEs exhibited an encapsulation efficiency of 88.30 ± 1.67%, which is greater than that of the AST-loaded SPI-stabilized NEs (AST-SPI-NEs) (77.31 ± 0.83%). Both AST-SPI-SA-NEs and AST-SPI-NEs exhibited significantly stronger hydroxyl or diphenylpicryl-hydrazyl radical-scavenging activities than the free AST. The formation of SPI-SA complexes strengthened the thermal, light, and storage stability of AST-SPI-SA-NEs with no apparently increasing mean diameter (around 200 nm). AST-SPI-SA-NEs also exhibited a better freeze-thaw dispersibility behavior than AST-SPI-NEs. AST-SPI-SA-NEs were more stable than AST-SPI-NEs were under in vitro gastrointestinal digestion conditions and exhibited a greater bioaccessibility (47.92 ± 0.42%) than both AST-SPI-NEs (12.97 ± 1.33%) and free AST (7.87 ± 0.37%). Hydrogen bonding was confirmed to participate in the formation of AST-SPI-SA-NEs and AST-SPI-NEs based on the molecular docking results. CONCLUSIONS: The construction of SPI-SA-NEs is conducive to the encapsulation, protection, and absorption of AST, providing a promising method for broadening the application of AST in processed foods or developing novel ingredients of functional foods. © 2023 Society of Chemical Industry.

Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study.

BACKGROUND: Evidence from observational studies and clinical trials suggests that the gut microbiota is associated with cancer. However, the causal association between gut microbiota and cancer remains to be determined. METHODS: We first identified two sets of gut microbiota based on phylum, class, order, family, and genus level information, and cancer data were obtained from the IEU Open GWAS project. We then performed two-sample Mendelian randomisation (MR) to determine whether the gut microbiota is causally associated with eight cancer types. Furthermore, we performed a bi-directional MR analysis to examine the direction of the causal relations. RESULTS: We identified 11 causal relationships between genetic liability in the gut microbiome and cancer, including those involving the genus Bifidobacterium. We found 17 strong associations between genetic liability in the gut microbiome and cancer. Moreover, we found 24 associations between genetic liability in the gut microbiome and cancer using multiple datasets. CONCLUSIONS: Our MR analysis revealed that the gut microbiota was causally associated with cancers and may be useful in providing new insights for further mechanistic and clinical studies of microbiota-mediated cancer.

AP4M1 as a prognostic biomarker associated with cell proliferation, migration and immune regulation in hepatocellular carcinoma.

BACKGROUND: AP4M1 is a protein-coding gene that plays a crucial role in transporter activity, recognition, and hereditary-associated diseases, but it's largely unknown in cancers. METHODS: The expression level of AP4M1 in cancers was investigated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the correlation between AP4M1 and hepatocellular carcinoma (HCC) clinicopathological parameters were analyzed. Univariate and multifactorial COX regression analyses were performed to clarify the prognostic value of AP4M1 in HCC. The correlation between AP4M1 and immune cell infiltration was analyzed using single-sample Gene Set Enrichment Analysis (ssGSEA). Besides, we verified the biological function of AP4M1 by applying Cell Counting Kit-8 (CCK8), colony formation, and transwell assays. RESULTS: The expression of AP4M1 was significantly elevated in HCC and was correlated with patients' pathological grades, AFP, and BMI. Kaplan-Meier survival curves indicated that patients with AP4M1 overexpression had worse overall survival. Univariate and multivariate COX regression analyses showed that AP4M1 was an independent risk factor affecting the prognosis of HCC. In addition, we observed that AP4M1 positively correlated with most immune checkpoint suppressor genes in HCC. Moreover, in vitro experiments further confirmed that AP4M1 could promote the proliferation and invasion of HCC. CONCLUSIONS: AP4M1 is highly expressed and associated with poor prognosis in HCC. AP4M1 is closely related to cancer-immune regulation and could be a novel target for HCC, and guiding new strategies for the diagnosis and treatment of HCC patients.

The deubiquitinase EIF3H promotes hepatocellular carcinoma progression by stabilizing OGT and inhibiting ferroptosis.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal human malignancies, and with quite limited treatment alternatives. The proteasome is responsible for most of the protein degradation in eukaryotic cells and required for the maintenance of intracellular homeostasis. However, its potential role in HCC is largely unknown. In the current study, we identified eukaryotic translation initiation factor 3 subunit H (EIF3H), belonging to the JAB1/MPN/MOV34 (JAMM) superfamily, as a bona fide deubiquitylase of O-GlcNAc transferase (OGT) in HCC. We explored that EIF3H was positively associated with OGT in HCC and was related to the unfavorable prognosis. EIF3H could interact with, deubiquitylate, and stabilize OGT in a deubiquitylase-dependent manner. Specifically, EIF3H was associated with the GT domain of ERα via its JAB/MP domain, thus inhibiting the K48-linked ubiquitin chain on OGT. Besides, we demonstrated that the knockdown of EIF3H significantly reduced OGT protein expression, cell proliferation and invasion, and caused G1/S arrest of HCC. We also found that the deletion of EIF3H prompted ferroptosis in HCC cells. Finally, the effects of EIF3H depletion could be reversed by further OGT overexpression, implying that the OGT status is indispensable for EIF3H function in HCC carcinogenesis. In summary, our study described the oncogenic function of EIF3H and revealed an interesting post-translational mechanism between EIF3H, OGT, and ferroptosis in HCC. Targeting the EIF3H may be a promising approach in HCC. Video Abstract.

Pembrolizumab plus lenvatinib as first-line therapy for patients with mismatch repair-proficient advanced endometrial cancer: A United States-based cost-effectiveness analysis.

OBJECTIVE: In 2022, the KEYNOTE-775 (NCT03517449) study showed that pembrolizumab plus lenvatinib (PL) has more benefits than traditional chemotherapy as a first-line regimen to treat patients with mismatch repair-proficient (pMMR) advanced endometrial cancer (aEC). However, given the high cost of immuno-targeted therapy, the widespread use among patients remains uncertain. Therefore, we conducted a cost-effectiveness comparison between PL and chemotherapy. METHODS: We evaluated the cost-effectiveness of PL versus chemotherapy over 7 years by developing a comprehensive Markov model, included 697 patients, that calculated total cost, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of $150,000 per QALY. The robustness of the model was evaluated by one-way, two-way, and probabilistic sensitivity analyses. In addition, we also performed subgroup analyses. RESULTS: Chemotherapy yielded a mean survival of 0.705 QALYs (0.901 LYs) per patient and was associated with a mean cost of $163,777. PL was associated with an incremental cost of $38,582 and an additional 0.349 QALYs, leading to an ICER of $110,401 per QALY as compared to chemotherapy. The cost of pembrolizumab had a significant impact on ICER. At the assumed WTP threshold of $150,000 per QALY, approximately 79.2% of simulations show cost-effectiveness occurs in PL. Results of the subgroup analysis showed that PL was the most cost-effective regimen for patients who had previously received 1-line of therapy. CONCLUSION: For patients with pMMR aEC, the PL strategy may be the most cost-effective strategy at a WTP of $150,000 from the economic perspective of the United States.

SUMOylation of methyltransferase-like 3 facilitates colorectal cancer progression by promoting circ_0000677 in an m6 A-dependent manner.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the major health issues in the world. Circ_0000677 has been shown to be upregulated in CRC with unclarified function and mechanism. Methyltransferase-like 3 (METTL3) acts as a regulator for gene expression via the mechanism of RNA N6 -methyladenosine (m6 A) in different types of cancer, which is under the control of SUMO1-based SUMOylation. We aim to investigate their roles in CRC progression. METHODS: Quantitative real-time polymerase chain reaction and Western blot were used to detect the expressions of METTL3, circ_0000677, and ATP binding cassette subfamily c member 1(ABCC1) in CRC patients' tissues and cell lines. The functions of ABCC1 and circ_0000677 in CRC were studied by manipulating their level via knocking down or overexpression. RNA pull-down and RNA immunoprecipitation assays were performed to identify the specific binding of target genes. The biological function of SUMOylation of METTL3 was investigated in vivo by xenograft mice tumor model. RESULTS: METTL3, circ_0000677, and ABCC1 were upregulated in CRC patients' samples and cell lines. Circ_0000677 positively regulates CRC cell proliferation and drug resistance via affecting ABCC1 expression. METTL3 facilitated circ_0000677 level via m6 A modification. METTL3 was regulated by SUMO1-mediated SUMOylation in CRC. Mutation of METTL3-K459 could suppress tumor growth in vivo via regulating circ_0000677/ABCC1 axis. CONCLUSIONS: Overall, our study revealed that circ_0000677 and its downstream target ABCC1 were upregulated in CRC cells, induced by the METTL3-mediated m6 A modification of circ_0000677 and SUMO1-mediated SUMOylation of METTL3. This work provided a new strategy for the therapeutic treatment of CRC.

Impact of Increased FUT8 Expression on the Extracellular Vesicle Proteome in Prostate Cancer Cells.

Extracellular vesicles (EVs) are involved in intercellular communication, transporting proteins and nucleic acids to proximal and distal regions. There is evidence of glycosylation influencing protein routing into EVs; however, the impact of aberrant cellular glycotransferase expression on EV protein profiles has yet to be evaluated. In this study, we paired extracellular vesicle characterization and quantitative proteomics to determine the systemic impact of altered α(1,6)fucosyltranferase (FUT8) expression on prostate cancer-derived EVs. Our results showed that increased cellular expression of FUT8 could reduce the number of vesicles secreted by prostate cancer cells as well as increase the abundance of proteins associated with cell motility and prostate cancer metastasis. In addition, overexpression of FUT8 resulted in altered glycans on select EV-derived glycoproteins. This study presents the first evidence of altered cellular glycosylation impacting EV protein profiles and provides further rationale for exploring the functional role of glycosylation in EV biogenesis and biology.

Glycans, Glycosite, and Intact Glycopeptide Analysis of N-Linked Glycoproteins Using Liquid Handling Systems.

Aberrant glycosylation has been shown to associate with disease progression, and with glycoproteins representing the major protein component of biological fluids this makes them attractive targets for disease monitoring. Leveraging glycoproteomic analysis via mass spectrometry (MS) could provide the insight into the altered glycosylation patterns that relate to disease progression. However, investigation of large sample cohorts requires rapid, efficient, and highly reproducible sample preparation. To address the limitation, we developed a high-throughput method for characterizing glycans, glycosites, and intact glycopeptides (IGPs) derived from N-linked glycoproteins. We combined disparate peptide enrichment strategies (i.e., hydrophilic and hydrophobic) and a liquid handling platform allowing for a high throughput and rapid enrichment of IGP in a 96-well plate format. The C18/MAX-Tip workflow reduced sample processing time and facilitated the selective enrichment of IGPs from complex samples. Furthermore, our approach enabled the analysis of deglycosylated peptides and glycans from enriched IGPs following PNGase F digest. Following development and optimization of the C18/MAX-Tip methodology using the standard glycoprotein, fetuin, we investigated normal urine samples to obtain N-linked glycoprotein information. Together, our method enables a high-throughput enrichment of glycan, glycosites, and IGPs from biological samples.

An Integrated Workflow for Global, Glyco-, and Phospho-proteomic Analysis of Tumor Tissues.

Recently, the rapid development and application of mass spectrometry (MS)-based technologies have markedly improved the comprehensive proteomic characterization of global proteome and protein post-translational modifications (PTMs). However, the current conventional approach for global proteomic analysis is often carried out separately from PTM analysis. In our study, we developed an integrated workflow for multiplex analysis of global, glyco-, and phospho-proteomics using breast cancer patient-derived xenograft (PDX) tumor samples. Our approach included the following steps: trypsin-digested tumor samples were enriched for phosphopeptides through immobilized metal ion affinity chromatography (IMAC), followed by enrichment of glycopeptides through mixed anion exchange (MAX) method, and then the flow-through peptides were analyzed for global proteomics. Our workflow demonstrated an increased identification of peptides and associated proteins in global proteome, as compared to those using the peptides without PTM depletion. In addition to global proteome, the workflow identified phosphopeptides and glycopeptides from the PTM enrichment. We also found a subset of glycans with unique distribution profiles in the IMAC flow-through, as compared to those enriched directly using the MAX method. Our integrated workflow provided an effective platform for simultaneous global proteomic and PTM analysis of biospecimens.

Gamma-phase CsPbBr3 perovskite nanocrystals/polymethyl methacrylate electrospun nanofibrous membranes with superior photo-catalytic property.

Gamma-phase cesium lead tri-bromide perovskite nanocrystals (γ-CsPbBr3 NCs) possess potentially photo-catalytic degradation ability and long-term stability. However, their serious aggregation issue decreases their active surface area, and the recombination of photo-generated hole-electron pairs weakens their photo-catalytic property. Furthermore, these NCs can be easily absorbed on the surface of dyes [e.g., methylene blue (MB)] or dissolved in the dye solution during the photo-catalytic degradation process, thus reducing the amount of γ-CsPbBr3 NCs and their photo-catalytic degradation ability. Besides, the residual γ-CsPbBr3 NCs in the photo-catalytic degradation products also present the toxicity issue (containing Pb) and are hazardous to the ecological environment and human health. In the present study, we fabricated γ-CsPbBr3 NCs/polymethyl methacrylate electrospun nanofibrous membranes (γ-CsPbBr3 NCs/PMMA ENMs) by using electrospinning technology to solve the above problems. It is found that the synthesized γ-CsPbBr3 NCs/PMMA ENMs show a large surface area and the abundant functional groups on their surfaces, which are benefit for forming multiple kinds of chemical bonding effect between γ-CsPbBr3 NCs and PMMA ENMs. In addition, γ-CsPbBr3 NCs could disperse homogeneously in or on the surface of PMMA ENMs. These abundant chemical bonds and homogeneous distributions of γ-CsPbBr3 NCs on the surface of PMMA ENMs can significantly decrease the recombination of photo-generated hole-electron pairs and toxicity issue of γ-CsPbBr3 NCs during the photo-catalytic degradation process. Exhilaratingly, γ-CsPbBr3 NCs/PMMA ENMs could maintain a superior photo-catalytic degradation ability toward various dyes and reveal a high photo-catalytic degradation efficiency of 99.18% in 60 min for MB.

Identification of CAV1 and DCN as potential predictive biomarkers for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histological form of lung cancer that is clinically diagnosed. The aim of this study is to explore the novel genes associated with LUAD tumorigenesis. Comprehensive bioinformatics analyses of the data were obtained from several publicly available databases, such as the Gene Expression Omnibus, the Human Protein Atlas project, and the Cancer Cell Line Encyclopedia. The clinical relevance of these novel genes in LUAD was further examined by immunohistochemistry. We identified the overlapping differentially expressed genes (DEGs) in five independent microarray data sets from the Gene Expression Omnibus database ( GSE75037 , GSE85716 , GSE85841 , GSE63459 , and GSE32867 ). Using the criteria of |log (fold change)| ≥ 1 and P value <0.05, 167 genes were preliminarily validated as co-DEGs. Protein-protein interaction network analysis indicated that caveolin 1 (CAV1) and decorin (DCN) levels were significantly reduced and that these genes were the most promising predictive biomarkers for the occurrence and prognosis of LUAD. A cell proliferation assay indicated that overexpressed CAV1 and DCN could significantly inhibit the proliferation rate of A549 and H157 cells. Additionally, these two downregulated candidate genes were further verified by immunohistochemistry conducted on a LUAD tissue array and comprehensive bioinformatics analyses, including those using the Oncomine platform and the Cancer Cell Line Encyclopedia. Our study demonstrates low levels of CAV1 and DCN in LUAD. An understanding of their functional roles in LUAD biology would give us important insights that would be useful in further investigations.

Simple Tip-Based Sample Processing Method for Urinary Proteomic Analysis.

Mass spectrometry-based urinary proteomics is one of the most attractive strategies to discover proteins for diagnosis, prognosis, monitoring, or prediction of therapeutic responses of urological diseases involving the kidney, prostate, and bladder; however, interfering compounds found in urine necessitate sample preparation strategies that are currently not suitable for urinary proteomics in the clinical setting. Herein, we describe the C4-tip method, comprising a simple, automated strategy utilizing a reverse-phase resin tip-based format and "on-tip" digestion to examine the urine proteome. We first determined the optimal conditions for protein isolation and protease digestion on the C4-tip using the standard protein bovine fetuin. Next, we applied the C4-tip method to urinary proteomics, identifying a total of 813 protein groups using LC-MS/MS, with identified proteins from the C4-tip method displaying a similar distribution of gene ontology (GO) cellular component assignments compared to identified proteins from an ultrafiltration preparation method. Finally, we assessed the reproducibility of the C4-tip method, revealing a high Spearman correlation R-value for shared proteins identified across all tips. Together, we have shown the C4-tip method to be a simple, robust method for high-throughput analysis of the urinary proteome by mass spectrometry in the clinical setting.

Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Because the prognosis of DLBCL patients varies considerably, there is an urgent need to identify novel prognostic factors. In this study, we investigated the expression levels of the signalling enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1), the cell cycle regulatory enzyme Polo-like kinase 1 (PLK1) and the transcription factor (c-Myc) in DLBCL tissues and evaluated their clinical and prognostic significance. PDK1, PLK1 and c-Myc were detected by immunohistochemical staining of paraffin-embedded specimens from 152 DLBCL and 48 lymphadenitis patients. Expression levels were correlated with clinicopathological factors. PDK1, PLK1 and c-Myc were more commonly expressed in DLBCL specimens than in lymphadenitis specimens, and the expression of each protein correlated positively with that of the other two molecules. High PDK1, PLK1 and c-Myc expression, high international prognostic index score, high lactate dehydrogenase levels and late Ann Arbor stage were shown to correlate with shorter overall survival time. A multivariate Cox regression model showed that high expression levels of PLK1 and c-Myc were independent prognostic factors for DLBCL. Our findings indicate that PLK1 and c-Myc expression might be promising predictive biomarkers for DLBCL patients.

Perovskite solar cells: must lead be replaced - and can it be done?

Perovskite solar cells have recently drawn significant attention for photovoltaic applications with a certified power conversion efficiency of more than 22%. Unfortunately, the toxicity of the dissolvable lead content in these materials presents a critical concern for future commercial development. This review outlines some criteria for the possible replacement of lead by less toxic elements, and highlights current research progress in the application of low-lead halide perovskites as optically active materials in solar cells. These criteria are discussed with the aim of developing a better understanding of the physio-chemical properties of perovskites and of realizing similar photovoltaic performance in perovskite materials either with or without lead. Some open questions and future development prospects are outlined for further advancing perovskite solar cells toward both low toxicity and high efficiency.

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells.

BACKGROUND/AIMS: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. METHODS: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). RESULTS: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. CONCLUSION: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

STAT3 mediates multidrug resistance of Burkitt lymphoma cells by promoting antioxidant feedback.

Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm. Although BL is relatively sensitive to chemotherapy, some patients do not respond to initial therapy or relapse after standard therapy, which leads to poor prognosis. The mechanisms underlying BL chemoresistance remain poorly defined. Here, we report a mechanism for the relationship between the phosphorylation of STAT3 on Tyr705 and BL chemoresistance. In chemoresistant BL cells, STAT3 was activated and phosphorylated on Tyr705 in response to the generation of the reactive oxygen species (ROS), which induced Src Tyr416 phosphorylation after multi-chemotherapeutics treatment. As a transcription factor, the elevated phosphorylation level of STAT3Y705 increased the expression of GPx1 and SOD2, both of which protected cells against oxidative damage. Our findings revealed that the ROS-Src-STAT3-antioxidation pathway mediated negative feedback inhibition of apoptosis induced by chemotherapy. Thus, the phosphorylation of STAT3 on Tyr705 might be a target for the chemo-sensitization of BL.

Identification of a novel prognostic signature based on vitamin metabolism clustering-related genes in lung adenocarcinoma.

Background: Vitamins, and their metabolic processes play essential regulatory roles in controlling proliferation, differentiation, and growth in carcinogenesis. However, the role of vitamin metabolism in lung adenocarcinoma (LUAD) has rarely been reported. Here, we established a novel prognostic model based on vitamin metabolism-related genes in LUAD. Methods: In this research, we aimed to identify vitamin metabolism associated with differentially expressed genes (DEGs) in LUAD utilizing The Cancer Genome Atlas (TCGA)-LUAD, GSE68465 and GSE72094 data. Unsupervised clustering classified patients into distinct subgroups. By utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis, vitamin metabolism-related genes could be used to construct prognostic model. Then the vitamin metabolism gene-related risk score (VRS) was calculated based on best cut-off splitting. Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC) analysis, univariate and multivariate Cox analyses, chemotherapeutic drugs sensitivity analysis, immune infiltration analysis and nomogram were conducted to verify our models' accuracy. Finally, CPS1 was identified as a relevant diagnostic marker using Random Forests algorithms, single-cell RNA sequencing data was used to confirm its expression. Results: We investigated the relationship between vitamin metabolism patterns, overall survival (OS), and immune infiltration levels of patients with LUAD. A prognostic signature consisting of 11 genes was developed, which was able to classify patients into high and low VRS groups. Through gene enrichment analysis, cell cycle was mainly enriched. Compared to the low VRS group, the high VRS group exhibited poorer OS, as demonstrated by the Kaplan-Meier survival analysis. Furthermore, VRS was identified as an independent predictor of poor prognosis and poor OS, as indicated by both univariate and multivariate Cox regression analyses. Additionally, a nomogram was constructed to improve the accuracy of survival predictions in LUAD patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. CPS1 was identified as a relevant diagnostic marker and the expression was also as confirmed by single-cell RNA sequencing data. Conclusions: Overall, our findings suggest that vitamin metabolism can influence the prognosis of LUAD patients, and our prognostic signature represents a potentially helpful resource for predicting patient outcomes and informing clinical decision-making.

Suppressing Halide Segregation via Pyridine-Derivative Isomers Enables Efficient 1.68 eV Bandgap Perovskite Solar Cells.

Light-induced phase segregation is one of the main issues restricting the efficiency and stability of wide-bandgap perovskite solar cells (WBG PSCs). Small organic molecules with abundant functional groups can passivate various defects, and therefore suppress the ionic migration channels for phase segregation. Herein, a series of pyridine-derivative isomers containing amino and carboxyl are applied to modify the perovskite surface. The amino, carboxyl, and N-terminal of pyridine in all of these molecules can interact with undercoordinated Pb2+ through coordination bonds and suppress halide ions migration via hydrogen bonding. Among them, the 5-amino-3-pyridine carboxyl acid (APA-3) treated devices win the champion performance, enabling an efficiency of 22.35% (certified 22.17%) using the 1.68 eV perovskite, which represents one of the highest values for WBG-PSCs. This is believed to be due to the more symmetric spatial distribution of the three functional groups of APA-3, which provides a better passivation effect independent of the molecular arrangement orientation. Therefore, the APA-3 passivated perovskite shows the slightest halide segregation, the lowest defect density, and the least nonradiative recombination. Moreover, the APA-3 passivated device retains 90% of the initial efficiency after 985 h of operation at the maximum power point, representing the robust durability of WBG-PSCs under working conditions.

Cemiplimab as Second-Line Therapy for Patients with Recurrent Cervical Cancer: A United States-based Cost-effectiveness Analysis.

INTRODUCTION: The efficacy of cemiplimab in recurrent cervical cancer has been demonstrated in the clinical trial EMPOWER-Cervical 1. However, its high price makes patients and clinicians hesitate to use it. Therefore, we designed a study to evaluate its cost-effectiveness. METHODS: We developed a Markov model based on phase III clinical trials to calculate the cost, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over 20 years with a willingness-to-pay (WTP) threshold of $150,000/QALY. The economic data included were obtained from official US government websites and published literature. Sensitivity analysis was used to determine the uncertainties associated with the model, and a subgroup analysis was performed. RESULTS: Compared with chemotherapy, cemiplimab produced an additional 0.597 QALYs (0.751 LYs), resulting in an ICER of $111,211.471/QALY in the United States. The cost of cemiplimab is the most influential factor in the model. The results of these models were robust in all sensitivity analyses. From the American public payers' perspective, subgroup analysis showed cemiplimab was a cost-effective regimen in patients with squamous cell carcinoma, adenocarcinoma, or programmed cell death ligand 1 (PD-L1) ≥ 1%. CONCLUSION: From the American public payers' perspective, cemiplimab is a cost-effective treatment option for second-line treatment of recurrent cervical cancer. Meanwhile, cemiplimab was a cost-effective treatment for patients with PD-L1 ≥ 1 and all histological types.