Targeting HSP47 for cancer treatment.

Heat shock protein 47 (HSP47) serves as an endoplasmic reticulum residing collagen-specific chaperone and plays an important role in collagen biosynthesis and structural assembly. HSP47 is encoded by the SERPINH1 gene, which is located on chromosome 11q13.5, one of the most frequently amplified regions in human cancers. The expression of HSP47 is regulated by multiple cellular factors, including cytokines, transcription factors, microRNAs, and circular RNAs. HSP47 is frequently upregulated in a variety of cancers and plays an important role in tumor progression. HSP47 promotes tumor stemness, angiogenesis, growth, epithelial-mesenchymal transition, and metastatic capacity. HSP47 also regulates the efficacy of tumor therapies, such as chemotherapy, radiotherapy, and immunotherapy. Inhibition of HSP47 expression has antitumor effects, suggesting that targeting HSP47 is a feasible strategy for cancer treatment. In this review, we highlight the function and expression of regulatory mechanisms of HSP47 in cancer progression and point out the potential development of therapeutic strategies in targeting HSP47 in the future.

An up-conversion fluorescence lateral-flow immunoassay for rapid detection of Daratumumab in serum protein electrophoresis clinical samples.

BACKGROUND: Daratumumab (DARA) is a commonly used monoclonal antibody (mAb) drug for the treatment of multiple myeloma (MM). Its appearance as a visible abnormal band in the γ-region of a serum protein electrophoresis (SPEP) gel may interfere with the SPEP result interpretation. With the advantages of portability and rapid testing capabilities, up-conversion fluorescence lateral-flow immunoassay (LFA) can be an ideal solution to detect DARA interference. METHODS: An up-conversion fluorescence LFA strip was designed and constructed to perform semi-quantitative DARA testing in clinical samples. The LFA strip test was evaluated for limit of detection (LOD), dynamic range, and analytical interference. RESULTS: To demonstrate the clinical utility of the LFA strip, 43 SPEP-positive patient serum samples were tested for the presence of DARA, and the results exactly matched the DARA usage history in patient medical records. CONCLUSIONS: The performance of the up-conversion fluorescence LFA strip meets the purpose of clarifying DARA interference in SPEP results. It may be used as an independent and objective confirmation of the presence of DARA in clinical samples. The LFA strip offers a cost-effective rapid on-site test to check for DARA interference alongside standard SPEP equipment, which significantly improves the interpretation of ambiguous SPEP results involving DARA, and does not intervene the current SPEP workflow in clinical laboratory practice.

Highly Selective Acetylene-to-Ethylene Electroreduction Over Cd-Decorated Cu Catalyst with Efficiently Inhibited Carbon-Carbon Coupling.

Electrochemical acetylene reduction (EAR) employing Cu catalysts represents an environmentally friendly and cost-effective method for ethylene production and purification. However, Cu-based catalysts encounter product selectivity issues stemming from carbon-carbon coupling and other side reactions. We explored the use of secondary metals to modify Cu-based catalysts and identified Cd decoration as particular effective. Cd decoration demonstrated a high ethylene Faradaic efficiency (FE) of 98.38 % with well-inhibited carbon-carbon coupling reactions (0.06 % for butadiene FE at -0.5 V versus reversible hydrogen electrode) in a 5 vol % acetylene gas feed. Notably, ethylene selectivity of 99.99 % was achieved in the crude ethylene feed during prolonged stability tests. Theoretical calculations revealed that Cd metal accelerates the water dissociation on neighboring Cu surfaces allowing more H* to participate in the acetylene semi-hydrogenation, while increasing the energy barrier for carbon-carbon coupling, thereby contributing to a high ethylene semi-hydrogenation efficiency and significant inhibition of carbon-carbon coupling. This study provides a paradigm for a deeper understanding of secondary metals in regulating the product selectivity of EAR electrocatalysts.

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay.

Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

Photocatalytic ethylene production by oxidative dehydrogenation of ethane with dioxygen on ZnO-supported PdZn intermetallic nanoparticles.

The selective oxidative dehydrogenation of ethane (ODHE) is attracting increasing attention as a method for ethylene production. Typically, thermocatalysts operating at high temperatures are needed for C-H activation in ethane. In this study, we describe a low temperature ( < 140 °C) photocatalytic route for ODHE, using O2 as the oxidant. A photocatalyst containing PdZn intermetallic nanoparticles supported on ZnO is prepared, affording an ethylene production rate of 46.4 mmol g-1 h-1 with 92.6% ethylene selectivity under 365 nm irradiation. When we employ a simulated shale gas feed, the photocatalytic ODHE system achieves nearly 20% ethane conversion while maintaining an ethylene selectivity of about 87%. The robust interface between the PdZn intermetallic nanoparticles and ZnO support plays a crucial role in ethane activation through a photo-assisted Mars-van Krevelen mechanism, followed by a rapid lattice oxygen replenishment to complete the reaction cycle. Our findings demonstrate that photocatalytic ODHE is a promising method for alkane-to-alkene conversions under mild conditions.

A dual-channel fluorescence probe for simultaneously visualizing cysteine and viscosity during drug-induced hepatotoxicity.

Cysteine (Cys), one of the important participants in protecting cells from oxidative stress, is closely associated with the occurrence and development of various diseases. Moreover, cell viscosity as a pivotal microenvironmental parameter has recently attracted increasing attention due to its dominant role in governing intracellular signal transduction and diffusion of reactive metabolites. Thus, simultaneous detection of Cys and viscosity is imperative for investigating their pathophysiological functions and cross-link. Herein we present a mitochondria-targetable dual-channel fluorescence probe ABDSP by grafting the acrylate modified pyridinium unit to dimethylaminobenzene. Whilst the probe is a seemingly simple, it could simultaneously discriminate Cys and viscosity in a fashion of distinguishable signals. Furthermore, the probe was successfully employed for visualizing mitochondrial Cys and viscosity, and probe into their cross-link during acetaminophen-induced hepatotoxicity.

Cancer-derived non-coding RNAs endow tumor microenvironment with immunosuppressive properties.

Non-coding RNAs (ncRNAs) have attracted extensive attention due to their vital roles in tumorigenesis and progression, especially in the immunotherapy resistance. Tumor immunotherapy resistance is a crucial factor hindering the efficacy of tumor treatments, which can be largely attributed to the immunosuppressive properties of tumor microenvironment. Current studies have revealed that cancer-derived ncRNAs are involved in the formation of tumor immunosuppressive microenvironment (TIME) through multiple ways. They not only promote the expression of immune checkpoint ligands (e.g., PD-L1, CD47, Gal-9, and CD276) on cancer cell surfaces, but also enhance the secretion of immunosuppressive cytokines (e.g., TGF-ß, IL-6, IL-10, VEGF, and chemokines). Cancer-derived ncRNAs could also be transferred into surrounding immune-related cells through extracellular vesicles, thereby inhibiting the cytotoxicity of CD8+ T cells and NK cells, restraining the DC-mediated antigen presentation, inducing the immunosuppressive phenotype transformation of TAMs and CAFs, and enhancing the immunosuppressive functions of Tregs and MDSCs. Herein, we summarize the roles of cancer-derived ncRNAs in regulating TIME formation and further explore their potential applications as prognostic biomarkers and immunotherapeutic targets, which will help us to address the TIME-mediated immunotherapy resistance in the future. This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.

Multimodal Tetrahedral DNA Nanoplatform for Surprisingly Rapid and Significant Treatment of Acute Liver Failure.

Acute liver failure (ALF) is a life-threatening disease associated with the rapid development of inflammatory storms, reactive oxygen species (ROS) level elevation, and hepatocyte necrosis, which results in high short-term mortality. Except for liver transplantation, no effective strategies are available for ALF therapy due to the rapid disease progression and narrow therapeutic time window. Therefore, there is an urgent demand to explore fast and effective modalities for ALF treatment. Herein, a multifunctional tetrahedral DNA nanoplatform (TDN) is constructed by incorporating the tumor necrosis factor-α siRNA (siTNF-α) through DNA hybridization and antioxidant manganese porphyrin (MnP4) via π-π stacking interaction with G-quadruplex (G4) for surprisingly rapid and significant ALF therapy. TDN-siTNF-α/-G4-MnP4 silences TNF-α of macrophages by siTNF-α and polarizes them to the anti-inflammatory M2 phenotype, providing appropriate microenvironments for hepatocyte viability. Additionally, TDN-siTNF-α/-G4-MnP4 scavenges intracellular ROS by MnP4 and TDN, protecting hepatocytes from oxidative stress-associated cell death. Furthermore, TDN itself promotes hepatocyte proliferation via modulating the cell cycle. TDN-siTNF-α/-G4-MnP4 shows almost complete liver accumulation after intravenous injection and exhibits excellent therapeutic efficacy of ALF within 2 h. The multifunctional DNA nanoformulation provides an effective strategy for rapid ALF therapy, expanding its application for innovative treatments for liver diseases. This article is protected by copyright. All rights reserved.

Cancer-associated fibroblasts in hematologic malignancies: elucidating roles and spotlighting therapeutic targets.

Hematologic malignancies comprise a diverse range of blood, bone marrow, and organ-related disorders that present significant challenges due to drug resistance, relapse, and treatment failure. Cancer-associated fibroblasts (CAFs) represent a critical component of the tumor microenvironment (TME) and have recently emerged as potential therapeutic targets. In this comprehensive review, we summarize the latest findings on the roles of CAFs in various hematologic malignancies, including acute leukemia, multiple myeloma, chronic lymphocytic leukemia, myeloproliferative neoplasms, and lymphoma. We also explore their involvement in tumor progression, drug resistance, and the various signaling pathways implicated in their activation and function. While the underlying mechanisms and the existence of multiple CAF subtypes pose challenges, targeting CAFs and their associated pathways offers a promising avenue for the development of innovative treatments to improve patient outcomes in hematologic malignancies.

Anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell immunotherapy.

Equipping multiple functionalities on adoptive effector cells is essential to overcome the complex immunological barriers in solid tumors for superior antitumor efficacy. However, current cell engineering technologies cannot endow these functionalities to cells within a single step because of the different spatial distributions of targets in one cell. Here, we present a core-shell anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) to achieve one-step multiplexing cell engineering for multifunctional cell construction. Through fusing with the M1 macrophage membrane, ARMFUL inserts an anti-CD47 (aCD47)-modified lipid shell onto the surface and simultaneously delivers colony-stimulating factor 1 receptor inhibitor BLZ945-loaded core into the cytoplasm. The surface-presenting aCD47 boosts macrophage's phagocytosis against the tumor by blocking CD47. The cytoplasm-located BLZ945 prompts its polarization resistance to M2 phenotype in the immunosuppressive microenvironment via inactivating the intracellular M2 polarization signaling pathway. This ARMFUL provides a versatile cell engineering platform to customize multimodal cellular functions for enhanced adoptive cell therapy.

Titania-Supported Cu-Single-Atom Catalyst for Electrochemical Reduction of Acetylene to Ethylene at Low-Concentrations with Suppressed Hydrogen Evolution.

Electrochemical acetylene reduction (EAR) is a promising strategy for removing acetylene from ethylene-rich gas streams. However, suppressing the undesirable hydrogen evolution is vital for practical applications in acetylene-insufficient conditions. Herein, Cu single atoms are immobilized on anatase TiO2 nanoplates (Cu-SA/TiO2 ) for electrochemical acetylene reduction, achieving an ethylene selectivity of ≈97% with a 5 vol% acetylene gas feed (Ar balance). At the optimal Cu-single-atom loading, Cu-SA/TiO2 is able to effectively suppress HER and ethylene over-hydrogenation even when using dilute acetylene (0.5 vol%) or ethylene-rich gas feeds, delivering a 99.8% acetylene conversion, providing a turnover frequency of 8.9 × 10-2  s-1 , which is superior to other EAR catalysts reported to date. Theoretical calculations show that the Cu single atoms and the TiO2 support acted cooperatively to promote charge transfer to adsorbed acetylene molecules, whilst also inhibiting hydrogen generation in alkali environments, thus allowing selective ethylene production with negligible hydrogen evolution at low acetylene concentrations.

LINC00659 cooperated with ALKBH5 to accelerate gastric cancer progression by stabilising JAK1 mRNA in an m6 A-YTHDF2-dependent manner.

BACKGROUND: N6-methyladenosine (m6 A) RNA modification is known as a common epigenetic regulation form in eukaryotic cells. Emerging studies show that m6 A in noncoding RNAs makes a difference, and the aberrant expression of m6 A-associated enzymes may cause diseases. The demethylase alkB homologue 5 (ALKBH5) plays diverse roles in different cancers, but its role during gastric cancer (GC) progression is not well known. METHODS: The quantitative real-time polymerase chain reaction, immunohistochemistry staining and western blotting assays were used to detect ALKBH5 expression in GC tissues and human GC cell lines. The function assays in vitro and xenograft mouse model in vivo were used to investigate the effects of ALKBH5 during GC progression. RNA sequencing, MeRIP sequencing, RNA stability and luciferase reporter assays were performed to explore the potential molecular mechanisms involved in the function of ALKBH5. RNA binding protein immunoprecipitation sequencing (RIP-seq), RIP and RNA pull-down assays were performed to examine the influence of LINC00659 on the ALKBH5-JAK1 interaction. RESULTS: ALKBH5 was highly expressed in GC samples and associated with aggressive clinical features and poor prognosis. ALKBH5 promoted the abilities of GC cell proliferation and metastasis in vitro and in vivo. The m6 A modification on JAK1 mRNA was removed by ALKBH5, which resulted in the upregulated expression of JAK1. LINC00659 facilitated ALKBH5 binding to and upregulated JAK1 mRNA depending on an m6 A-YTHDF2 manner. Silencing of ALKBH5 or LINC00659 disrupted GC tumourigenesis via the JAK1 axis. JAK1 upregulation activated the JAK1/STAT3 pathway in GC. CONCLUSION: ALKBH5 promoted GC development via upregulated JAK1 mRNA expression mediated by LINC00659 in an m6 A-YTHDF2-dependent manner, and targeting ALKBH5 may be a promising therapeutic method for GC patients.

Plasmonic Cu Nanoparticles for the Low-temperature Photo-driven Water-gas Shift Reaction.

The activation of water molecules in thermal catalysis typically requires high temperatures, representing an obstacle to catalyst development for the low-temperature water-gas shift reaction (WGSR). Plasmonic photocatalysis allows activation of water at low temperatures through the generation of light-induced hot electrons. Herein, we report a layered double hydroxide-derived copper catalyst (LD-Cu) with outstanding performance for the low-temperature photo-driven WGSR. LD-Cu offered a lower activation energy for WGSR to H2 under UV/Vis irradiation (1.4 W cm-2 ) compared to under dark conditions. Detailed experimental studies revealed that highly dispersed Cu nanoparticles created an abundance of hot electrons during light absorption, which promoted *H2 O dissociation and *H combination via a carboxyl pathway, leading to the efficient production of H2 . Results demonstrate the benefits of exploiting plasmonic phenomena in the development of photo-driven low-temperature WGSR catalysts.

Peripheral blood lymphocytes differentiation patterns in responses / outcomes to immune checkpoint blockade therapies in non-small cell lung cancer: a retrospective study.

OBJECTIVES: Programmed Cell Death-1/ Programmed Death-ligand 1 (PD-1 / PD-L1) inhibitor therapies targeting immunocytes induce persistent tumor remission in various cancers. However, the appropriate biomarkers for the therapeutic efficacy of PD-L1 and PD-1 blockade remain elusive. MATERIALS AND METHODS: For a comprehensive analysis of peri-treatment lymphocyte differentiation, in the current study, we enrolled 146 non-small cell lung cancer patients who received α-PD-1 therapies for exploring the peripheral blood lymphocyte differentiation pattern at baseline and post-treatment (dynamic changes) by flow cytometry. RESULTS: At baseline, CD4+ / CD8+ T cell ratio predicts good responses and outcomes, but activated T cell and cytotoxic T cell counts predict poor responses and outcomes. And for dynamic changes, after 6 weeks of immune checkpoint blockade (ICB) treatment, compared with baseline level, the elevation of total T and B cell counts indicate poor responses, and total T and TH cell counts indicate poor prognosis while activated T cell predicts good prognosis. And after 12 weeks, elevated total lymphocyte, cytotoxic T cell counts, and decreased total T cell counts and CD4+ / CD8+ T cell ratio predict good responses / outcomes. Our clinical predicting model shows good performance in predicting ICB treatment responses / outcomes. CONCLUSION: Patients with favorable clinical responses / outcomes have distinctive peripheral blood immunocyte differentiation characteristics, indicating the potential of utilizing the peripheral immunocyte differentiation patterns for predicting ICB responses / outcomes.

Pharmacokinetic characteristics of emodin in polygoni Multiflori Radix Praeparata.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygoni Multiflori Radix Praeparata (Zhiheshouwu) has been a Wudang Taoist medicine for tonifying the liver and kidney, resolving turbidity and reducing lipid. Emodin is one of the active anthraquinones in Zhiheshouwu. Our previous studies showed that emodin (EM) and the other anthraquinones in Zhiheshouwu extract (HSWE) exerted similar inhibitory effects on liver cancer cells in vitro. However, it is still unknown if the other anthraquinones enhance pharmacokinetics (PK) of EM in HSWE in vivo. AIM OF THE STUDY: In this study, we compared the PK characteristics of EM alone with that in Zhiheshouwu aiming to explore which anthraquinones in HSWE contribute to the changed PK of EM in rats. MATERIALS AND METHODS: Quality control of HSWE was determined using high performance liquid chromatography (HPLC). The ratios of emodin to other anthraquinones, physcion (PH), chrysophanol (CH), rhein (RH), aloe-emodin (AE), emodin-8-O-ß-D-glycoside (EMG), physcion-1-O-ß-D-glycoside (PHG) and chrysophanol-8-O-ß-D-glycoside (CHG) in HSWE were determined and analyzed using UPLC combined with tandem mass spectrometry (UPLC/MS). The PK parameters and intestinal tissue concentration of EM alone, EM in HSWE, or with other anthraquinones in SD rats were analyzed using UPLC/MS. RESULTS: The quality of the Zhiheshouwu samples met the quality standard of the Chinese Pharmacopoeia (Version 2020). The PK results showed that compared with EM alone, Cmax (239.90 ± 146.71 vs. 898.46 ± 291.62, P < 0.001), Tmax (0.26 ± 0.15 vs. 12.55 ± 1.33, P < 0.001), AUC0-t (1575.09 ± 570.46 vs. 12154.96 ± 5394.25, P < 0.001), and AUC0-∞ (4742.51 ± 1837.62 vs. 37131.34 ± 21647.39, P < 0.001) of EM in HSWE were decreased due to PH and EMG, while the values of Vd (380.75 ± 217.74 vs. 11.75 ± 7.35, P < 0.001), T1/2 (10.81 ± 1.99 vs. 6.65 ± 2.76, P < 0.05) and CL (19.30 ± 7.82 vs. 2.78 ± 1.88, P < 0.001) of EM in HSWE were increased due to PH and AE. In addition, the intestinal tissue concentration of emodin in HSWE was decreased compared with that of EM alone in 20 and 780 min (25.37 ± 5.98 vs. 43.29 ± 4.16 and 26.72 ± 4.03 vs. 43.40 ± 14.19, respectively. P < 0.05) dominantly due to RH and PH. CONCLUSION: In conclusion, compared with treatment of EM alone, the AUC0-t value of EM in HSWE was decreased with different ways in rats. PH shortened Tmax, and increased Vd and CL. While AE prolonged T1/2 of EM. This indicated that the other anthraquinones in HSWE changed the PK of EM in rats and participated in the complex effects of EM on liver cancer. Besides the other anthraquinones, other components (e.g., 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside) in Zhiheshouwu may contribute in the pharmacokinetic and pharmacodynamic interactions with EM for anti-liver cancer.

Pro-prion, as a membrane adaptor protein for E3 ligase c-Cbl, facilitates the ubiquitination of IGF-1R, promoting melanoma metastasis.

Aberrant activation of receptor tyrosine kinase (RTK) is usually a result of mutation and plays important roles in tumorigenesis. How RTK without mutation affects tumorigenesis remains incompletely understood. Here we show that in human melanomas pro-prion (pro-PrP) is an adaptor protein for an E3 ligase c-Cbl, enabling it to polyubiquitinate activated insulin-like growth factor-1 receptor (IGF-1R), leading to enhanced melanoma metastasis. All human melanoma cell lines studied here express pro-PrP, retaining its glycosylphosphatidylinositol-peptide signal sequence (GPI-PSS). The sequence, PVILLISFLI in the GPI-PSS of pro-PrP, binds c-Cbl, docking c-Cbl to the inner cell membrane, forming a pro-PrP/c-Cbl/IGF-1R trimeric complex. Subsequently, IGF-1R polyubiquitination and degradation are augmented, which increases autophagy and tumor metastasis. Importantly, the synthetic peptide PVILLISFLI disrupts the pro-PrP/c-Cbl/IGF-1R complex, reducing cancer cell autophagy and mitigating tumor aggressiveness in vitro and in vivo. Targeting cancer-associated GPI-PSS may provide a therapeutic approach for treating human cancers expressing pro-PrP.

Adjuvant effects of Chinese medicinal tonics on gastric, liver, and colorectal cancers-OMICs-based contributions to understanding their mechanism of action.

Gastric, liver, and colorectal cancers belong to gastrointestinal (GI) cancers, one of the most threatening diseases in the world. The tonics class in Chinese medicines plays a critical role in antigastrointestinal cancer as adjuvants. However, it is a challenge to study the effects and underlying mechanisms of tonics due to their multiple components and multiple targets; OMICs were introduced to facilitate the investigation of the complex mixture of tonics. In this review, the online databases PubMed, ProQuest, Web of Knowledge, China National Knowledge Infrastructure (CNKI), Chongqing VIP, and Wanfang were retrieved from 1 January 2011 to 31 May 2022, in an aim to summarize and discuss the research progress of the effects and, especially, the underlying mechanisms of tonics for antigastrointestinal cancers via OMICs. The results showed that through the combination of OMICs and other technologies, tonics have been used for gastrointestinal cancer by targeting cancer hallmarks, enhancing body resistance to carcinogenesis, enhancing therapeutic effects, and/or decreasing side effects. In conclusion, tonics may play a promising role in gastric, liver, and colorectal cancers as adjuvants and can be well investigated via the combination of OMICs and other technologies, which deserves further study.

Targeting pancreatic stellate cells in chronic pancreatitis: Focus on therapeutic drugs and natural compounds.

Chronic pancreatitis (CP) is a precancerous illness linked to pancreatic ductal adenocarcinoma (PDAC), although the evolutionary mechanism is uncertain. CP is distinguished by severe fibrosis caused by the activation of pancreatic stellate cells (PSCs). The current clinical therapeutic protocol for CP lacks specific therapeutic medicines for the prevention and suppression of inflammation and fibrosis aggravating in CP. More research on specifically targeting PSCs would help facilitate the development of novel therapies for pancreatic fibrosis. Notably, using natural compounds from medicinal plants as new antifibrotic agents has become a focus of recent research and is widely employed as an alternative and complementary approach. Our goal was to shed light on the role of PSCs in the development of CP and provide a focused update on the new potential therapeutic strategies against PSCs in CP models. Future studies can refer to these possible strategies for drug design, bioavailability, pharmacokinetics, and other issues to obtain better clinical outcomes for treating CP.

Thermal-Radiation-Driven Ultrafast Crystallization of Perovskite Films Under Heavy Humidity for Efficient Inverted Solar Cells.

Fabricating perovskite solar cells (PSCs) in air is conducive to low-cost commercial production; nevertheless, it is rather difficult to achieve comparable device performance as that in an inert atmosphere because of the poor moisture toleration of perovskite materials. Here, the perovskite crystallization process is systematically studied using two-step sequential solution deposition in an inert atmosphere (glovebox) and air. It is found that moisture can stabilize solvation intermediates and prevent their conversion into perovskite crystals. To address this issue, thermal radiation is used to accelerate perovskite crystallization for integrated perovskite films within 10 s in air. The as-formed perovskite films are compact, highly oriented with giant grain size, superior photoelectric properties, and low trap density. When the films are applied to PSC devices, a champion power conversion efficiency (PCE) of 20.8% is obtained, one of the best results for air-processed inverted PSCs under high relative humidity (60 ± 10%). This work substantially assists understanding and modulation to perovskite crystallization kinetics under heavy humidity. Also, the ultrafast conversion strategy by thermal radiation provides unprecedented opportunities to manufacture high-quality perovskite films for low-temperature, eco-friendly, and air-processed efficient inverted PSCs.

APOBEC-mediated mutagenesis is a favorable predictor of prognosis and immunotherapy for bladder cancer patients: evidence from pan-cancer analysis and multiple databases.

Background: The APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family-mediated mutagenesis is widespread in human cancers. However, our knowledge of the biological feature and clinical relevance of APOBECs and APOBEC mutagenesis in cancers remains limited. Methods: In this study, with a series of bioinformatic and statistical approaches, we performed a comprehensive analysis of multiple levels of data, including whole-exome sequencing (WES) and targeted next-generation sequencing (NGS), transcriptome (bulk RNA-seq and single-cell RNA-seq), immune signatures and immune checkpoint blockade (ICB) potential, patient survival and drug sensitivity, to reveal the distribution characteristics and clinical significance of APOBECs and APOBEC mutagenesis in pan-cancer especially bladder cancer (BLCA). Results: APOBEC mutagenesis dominates in the mutational patterns of BLCA. A higher enrichment score of APOBEC mutagenesis correlates with favorable prognosis, immune activation and potential ICB response in BLCA patients. APOBEC3A and 3B play a significant role in the malignant progression and cell differentiation within the tumor microenvironment. Furthermore, using machine learning approaches, a prognostic APOBEC mutagenesis-related model was established and validated in different BLCA cohorts. Conclusions: Our study illustrates the characterization of APOBECs and APOBEC mutagenesis in multiple cancer types and highlights its potential value as a promising biomarker for prognosis and immunotherapy in BLCA.