Oxygen vacancy induced defect dipoles in BiVO4 for photoelectrocatalytic partial oxidation of methane.

A strong driving force for charge separation and transfer in semiconductors is essential for designing effective photoelectrodes for solar energy conversion. While defect engineering and polarization alignment can enhance this process, their potential interference within a photoelectrode remains unclear. Here we show that oxygen vacancies in bismuth vanadate (BiVO4) can create defect dipoles due to a disruption of symmetry. The modified photoelectrodes exhibit a strong correlation between charge separation and transfer capability and external electrical poling, which is not seen in unmodified samples. Applying poling at -150 Volt boosts charge separation and transfer efficiency to over 90%. A photocurrent density of 6.3 mA cm-2 is achieved on the photoelectrode after loading with a nickel-iron oxide-based cocatalyst. Furthermore, using generated holes for methane partial oxidation can produce methanol with a Faradaic efficiency of approximately 6%. These findings provide valuable insights into the photoelectrocatalytic conversion of greenhouse gases into valuable chemical products.

Single-Atom Catalysts with p-Block Metals Surpass Transition-Metal Counterparts in the Photocatalytic H2O2 Production.

Growing interest in p-block metal single-atom catalysts (PM-SACs) is driven by their low toxicity, economic viability, and transition metal-like catalytic properties. However, selection criteria for p-block single-atom species and catalytic mechanisms of PM-SACs remain unclear. This study explores the catalytic abilities of PM-SACs and their transition metal counterparts (TM-SACs) based on polymetric carbon nitride (PCN) for photocatalytic hydrogen peroxide (H2O2) production. Using thermodynamic barriers as a key descriptor, it was found that PM-SACs can surpass TM-SACs in H2O2 production due to a lower energy barrier for *OOH intermediate formation resulting from optimized p-p hybridization. Specifically, Sb-SAC based on PCN shows the highest apparent quantum yield of 35.3 % at 400 nm. This study offers a rationale for the utilization of p-block SACs in the context of sustainable chemical synthesis.

Platinum Single-Atom Nests Boost Solar-Driven Photocatalytic Non-Oxidative Coupling of Methane to Ethane.

This work introduces a new strategy of a single-atom nest catalyst, whereby several single atoms are positioned closely, aiming to achieve the dual benefits of high atom-utilization efficiency while avoiding the steric hindrance in the coupling reaction. As a proof of concept, Pt single-atom nests, where the adjacent Pt single atoms are approximately 4 Å apart, are precisely engineered on the TiO2 photocatalyst for photocatalytic non-oxidative coupling of methane. The Pt single-atom nest photocatalyst demonstrates remarkable activity, achieving a C2H6 yield and turnover frequency of 251.6 µmol gcat-1 h-1 and 20 h-1, respectively, representing a 3.2-fold improvement compared to the Pt single-atom photocatalyst. Density functional theory calculations reveal that the Pt single-atom nest can significantly decrease the energy barrier for the activation of both CH4 molecules in the coupling process.

Oxygen Vacancy: How Will Poling History Affect Its Role in Photoelectrocatalysis.

Oxygen vacancy (VO) has been recognized to possess an effect to promote the charge separation and transfer (CST) in various n-type semiconductor based photoelectrodes. But how external stimulus will change this VO effect has not been investigated. In this work, external polarization is applied to investigate the effect of VO on the CST process of a typical ferroelectric BiFeO3 photoelectrode. It is found that negative poling treatment can significantly boost VO effect, while positive poling treatment will deteriorate the CST capability in BiFeO3 photoelectrodes. This poling history determined VO effect is rooted in the VO induced defect dipoles, wherein their alignment produces a depolarization electric field to modulate the CST driving force. This finding highlights the significance of poling history in functionalizing the VO in a photoelectrode.

Anti-angiogenic therapy or immunotherapy? A real-world study of patients with advanced non-small cell lung cancer with EGFR/HER2 exon 20 insertion mutations.

Background: For patients with EGFR/HER2 exon20 insertions, platinum-containing double-drug chemotherapy is still the standard treatment method. First-generation TKIs have almost no therapeutic activity against EGFR exon 20 insertions. The efficacy of second-and third-generation TKIs is still controversial. Immunotherapy research is scarce, and there is an urgent need for more evidence and new treatment options for this group of patients. Methods: We reviewed patients with advanced NSCLC with EGFR/HER2 exon 20 insertion mutations treated in Shanghai Chest Hospital and Shanghai Pulmonary Hospital from 2015 to 2022 and assessed the efficacy of receiving chemotherapy, anti-angiogenic therapy and immunotherapy, including objective response rate (ORR) and disease control rate (DCR), and compared progression-free survival (PFS) and overall survival (OS). Results: Of the 126 patients included in the study, 51 patients had EGFR20ins mutations and 7 5 patients had HER2-20ins mutations. In the first-line treatment, bevacizumab + chemotherapy (Beva+Chemo), ICI+chemotherapy (ICI+Chemo), compared with chemotherapy alone (Chemo), ORR: 40% vs 33.3% vs 15% (p=0.0168); DCR: 84% vs 80.9% vs 67.5% (p=0.1817); median PFS: 8.3 vs 7.0 vs 4.6 months (p=0.0032), ICI+Chemo has a trend of benefiting on OS. Stratified analysis showed that compared with chemotherapy, ICI+Chemo was more effective for EGFR20ins mutation with median PFS: 10.3 vs. 6.3m (P=0.013); Beva+Chemo was more effective for HER2-20ins mutation, with a median PFS: 6.6 vs. 4.3m (p=0.030). In the second-line treatment of EGFR20ins mutation, bevacizumab + chemotherapy has a significant advantage in PFS compared with targeted therapy, median PFS:10.8 vs 4.0 months (P=0.016). Conclusion: For patients with EGFR20ins mutation, compared to chemotherapy, ICI+Chemo prolongs PFS, and after chemotherapy progression, bevacizumab combined with chemotherapy seems better than Furmonertinib-based targeted therapy on PFS. For HER2-20ins mutation, Beva+Chemo may be a better choice.

Single-cell RNA-sequencing uncovers the dynamic changes of tumour immune microenvironment in advanced lung adenocarcinoma.

BACKGROUND: The heterogeneity of lung adenocarcinoma (LUAD) plays a vital role in determining the development of cancer and therapeutic sensitivity and significantly hinders the clinical treatment of LUAD. OBJECTIVE: To elucidate the cellular composition and reveal previously uncharacterised tumour microenvironment in LUAD using single-cell RNA-sequencing (scRNA-seq). METHODS: Two scRNA-seq datasets with 106 829 high-quality cells from 34 patients including 11 normal, 9 early (stage I and II) and 14 advanced (stage III and IV) LUAD were integrated and clustered to explore diagnostic and therapeutic cell populations and their biomarkers for diverse stages of LUAD. Three independent bulk RNA-seq datasets were used to validate the results from scRNA-seq analysis. The expression of marker genes for specific cell types in early and advanced LUAD was verified by immunohistochemistry (IHC). RESULTS: Comprehensive cluster analysis identified that S100P+ epithelial and SPP1+ macrophage, positively related to poor outcomes, were preferentially enriched in advanced stage. Although the accumulation of KLRB1+CD8+ T cell and IGHA1+/IGHG1+ plasma cell both significantly associated the favourable prognosis, we also found KLRB1+CD8+ T cell decreased in advanced stage while IGHA1+/IGHG1+ plasma cells were increased. Cell-cell communication analysis showed that SPP1+ macrophage could interact with most of CD8+ subclusters through SPP1-CD44 axis. Furthermore, based on three independent bulk RNA-seq datasets, we built risk model with nine marker genes for specific cell subtypes and conducted deconvolution analysis, both supporting our results from scRNA-seq data. We finally validated the expression of four marker genes in early and advanced LUAD by IHC. CONCLUSION: Our analyses highlight the molecular dynamics of LUAD epithelial and microenvironment and provide new targets to improve LUAD therapy.

Ultrabroadband plasmon driving selective photoreforming of methanol under ambient conditions.

Liquid methanol has the potential to be the hydrogen energy carrier and storage medium for the future green economy. However, there are still many challenges before zero-emission, affordable molecular H2 can be extracted from methanol with high performance. Here, we present noble-metal-free Cu-WC/W plasmonic nanohybrids which exhibit unsurpassed solar H2 extraction efficiency from pure methanol of 2,176.7 µmol g-1 h-1 at room temperature and normal pressure. Macro-to-micro experiments and simulations unveil that local reaction microenvironments are generated by the coperturbation of WC/W's lattice strain and infrared-plasmonic electric field. It enables spontaneous but selective zero-emission reaction pathways. Such microenvironments are found to be highly cooperative with solar-broadband-plasmon-excited charge carriers flowing from Cu to WC surfaces for efficient stable CH3OH plasmonic reforming with C3-dominated liquid products and 100% selective gaseous H2. Such high efficiency, without any COx emission, can be sustained for over a thousand-hour operation without obvious degradation.

Transient targeting of BIM-dependent adaptive MCL1 preservation enhances tumor response to molecular therapeutics in non-small cell lung cancer.

Despite remarkable efficacy, targeted treatments often yield a subpopulation of residual tumor cells in part due to non-genetic adaptions. Previous mechanistic understanding on the emergence of these drug-tolerant persisters (DTPs) has been limited to epigenetic and transcriptional reprogramming. Here, by comprehensively interrogating therapy-induced early dynamic protein changes in diverse oncogene-addicted non-small cell lung cancer models, we identified adaptive MCL1 increase as a new and universal mechanism to confer apoptotic evasion and DTP formation. In detail, acute MAPK signaling disruption in the presence of genotype-based tyrosine kinase inhibitors (TKIs) prompted mitochondrial accumulation of pro-apoptotic BH3-only protein BIM, which sequestered MCL1 away from MULE-mediated degradation. A small-molecule combination screen uncovered that PI3K-mTOR pathway blockade prohibited MCL1 upregulation. Biochemical and immunocytochemical evidence indicated that mTOR complex 2 (mTORC2) bound and phosphorylated MCL1, facilitating its interaction with BIM. As a result, short-term polytherapy combining antineoplastic TKIs with PI3K, mTOR or MCL1 inhibitors sufficed to prevent DTP development and promote cancer eradication. Collectively, these findings support that upfront and transient targeting of BIM-dependent, mTORC2-regulated adaptive MCL1 preservation holds enormous promise to improve the therapeutic index of molecular targeted agents.

Efficacy of alectinib in lung adenocarcinoma patients with different anaplastic lymphoma kinase (ALK) rearrangements and co-existing alterations-a retrospective cohort study.

Background: Alectinib significantly improves survival of non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK)-rearrangement. In this study, we analyzed the effects of different ALK rearrangements and co-mutations on the efficacy of alectinib. Methods: Using the electronic medical record system, we reviewed in terms of clinical and pathological features patients with advanced (IIIB/IV stage) ALK-rearranged NSCLC at Shanghai Chest Hospital between January 2018 and December 2021 who were treated with alectinib in first or second line and were assessed for objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 66 patients were enrolled in the study, and 17 types of ALK rearrangements were detected, of which five types of ALK rearrangements responded well to alectinib. We classified ALK-rearrangements into four main types, namely echinoderm microtubule-associated protein-like 4 (EML4)-ALK (E6:A20), EML4-ALK (E13:A20), EML4-ALK (E20:A20), and others. There was no significant difference in ORR and DCR of these types (ORR: 31.3% vs. 13.0% vs. 18.2% vs. 17.6%, P=0.575; DCR: 93.8% vs. 95.6% vs. 100.0% vs. 88.2%, P=0.627). The 3-year PFS rates were 25.0% (4/16) vs. 13.0% (3/23) vs. 27.3% (3/11) vs. 18.8% (3/16) for EML4-ALK (E6:A20), EML4-ALK (E13:A20), EML4-ALK (E20:A20), and others, respectively (P=0.725). The results of co-mutation analysis showed that the median PFS (mPFS) for patients with tumors harboring TP53 mutations was 30.4 months, significantly shorter than that of patients with tumors without co-mutations and whose mPFS was not mature (P=0.026). TSC1 co-mutation was also identified as a detrimental factor in outcome, with a DCR of 60% vs. 100% (P=0.031), mPFS of 30.4 months vs. not applicable (P=0.160) in patients with vs. those without this co-mutation, respectively. The efficacy of alectinib in patients with brain metastases is comparable to that in patients without distant organ metastases. There were two cases with specific fusion types that also responded to alectinib; namely, double ALK-rearrangements: EML4-ALK (E13:A20) and MSH2-ALK (M7:A20), and with a rare fusion partner, SPECC1L-ALK (S8:A20). Their PFS were 8.7 and 38.0 months, respectively. Conclusions: In this study, the efficacy of alectinib in different types of ALK-rearrangements varied slightly. TP53 and TSC1 co-mutations were identified as detrimental factors affecting efficacy. This study provides references for the response to alectinib in patients with different types of ALK rearrangements and co-mutation.

Floating perovskite-BiVO4 devices for scalable solar fuel production.

Photoelectrochemical (PEC) artificial leaves hold the potential to lower the costs of sustainable solar fuel production by integrating light harvesting and catalysis within one compact device. However, current deposition techniques limit their scalability1, whereas fragile and heavy bulk materials can affect their transport and deployment. Here we demonstrate the fabrication of lightweight artificial leaves by employing thin, flexible substrates and carbonaceous protection layers. Lead halide perovskite photocathodes deposited onto indium tin oxide-coated polyethylene terephthalate achieved an activity of 4,266 µmol H2 g-1 h-1 using a platinum catalyst, whereas photocathodes with a molecular Co catalyst for CO2 reduction attained a high CO:H2 selectivity of 7.2 under lower (0.1 sun) irradiation. The corresponding lightweight perovskite-BiVO4 PEC devices showed unassisted solar-to-fuel efficiencies of 0.58% (H2) and 0.053% (CO), respectively. Their potential for scalability is demonstrated by 100 cm2 stand-alone artificial leaves, which sustained a comparable performance and stability (of approximately 24 h) to their 1.7 cm2 counterparts. Bubbles formed under operation further enabled 30-100 mg cm-2 devices to float, while lightweight reactors facilitated gas collection during outdoor testing on a river. This leaf-like PEC device bridges the gulf in weight between traditional solar fuel approaches, showcasing activities per gram comparable to those of photocatalytic suspensions and plant leaves. The presented lightweight, floating systems may enable open-water applications, thus avoiding competition with land use.

mTOR pathway gene mutations predict response to immune checkpoint inhibitors in multiple cancers.

BACKGROUND: mTOR pathway is known to promote cancer malignancy and influence cancer immunity but is unknown for its role in immune checkpoint inhibitors (ICI) therapy. METHODS: Using Memorial Sloan-Kettering Cancer Center dataset (MSKCC), we extracted mTOR pathway gene mutations for stepwise Cox regression in 1661 cancer patients received ICI. We associated the mutation of the gene signature resulted from the stepwise Cox regression with the 1661 patients' survival. Other 553 ICI-treated patients were collected from 6 cohorts for validation. We also performed this survival association in patients without ICI treatment from MSKCC as discovery (n = 2244) and The Cancer Genome Atlas (TCGA) as validation (n = 763). Pathway enrichment analysis were performed using transcriptome profiles from TCGA and IMvigor210 trial to investigate the potential mechanism. RESULTS: We identified 8 genes involved in mTOR pathway, including FGFR2, PIK3C3, FGFR4, FGFR1, FGF3, AKT1, mTOR, and RPTOR, resulted from stepwise Cox regression in discovery (n = 1661). In both discovery (n = 1661) and validation (n = 553), the mutation of the 8-gene signature was associated with better survival of the patients treated with ICI, which was independent of tumor mutation burden (TMB) and mainly attributed to the missense mutations. This survival association was not observed in patients without ICI therapy. Intriguingly, the mutation of the 8-gene signature was associated with increased TMB and PD1/PD-L1 expression. Immunologically, pathways involved in anti-tumor immune response were enriched in presence of this mutational signature in mTOR pathway, leading to increased infiltration of immune effector cells (e.g., CD8 + T cells, NK cells, and M1 macrophages), but decreased infiltration of immune inhibitory M2 macrophages. CONCLUSIONS: These results suggested that mTOR pathway gene mutations were predictive of better survival upon ICI treatment in multiple cancers, likely by its association with enhanced anti-tumor immunity. Larger studies are warranted to validate our findings.

An Experimentally Verified LC-MS Protocol toward an Economical, Reliable, and Quantitative Isotopic Analysis in Nitrogen Reduction Reactions.

To substitute the energy-intensive Haber-Bosch process for the synthesis of ammonia, some labile techniques, such as photocatalysis, electrocatalysis, photoelectrocatalysis, and photothermocatalysis, have emerged and attracted intense research interest. However, the contamination of the reaction system is one of the major concerns on how to reliably and accurately evaluate the performance of these catalysts, which is why various control studies are involved. Isotopic labeling studies are one of the most reliable control strategies in nitrogen fixation experiments, to ensure that N2 is exclusively the source of the generated ammonia. As a convenient, sensitive and accurate technique distinguished with a quantitative atomic mass resolution, liquid chromatography-mass spectrometry (LC-MS) has been extensively employed for the detection of ammonia in aqueous electrolyte systems. However, the previous work protocols for 15 N2 isotopic analysis using LC-MS either involved hazardous procedures which could potentially damage the instrument, or lacked in their experimental verification using real samples. Herein, a safe, reproducible and economical protocol for the detection of ammonia using LC-MS is presented, exhibiting an exponentially steep progressive detectivity of 15 N abundance, well verified with a series of experimental results for nitrogen reduction reactions. This is expected to provide a prudent cost-effective and sustainable gateway into isotopic analysis.

Noble-Metal-Free Multicomponent Nanointegration for Sustainable Energy Conversion.

Global energy and environmental crises are among the most pressing challenges facing humankind. To overcome these challenges, recent years have seen an upsurge of interest in the development and production of renewable chemical fuels as alternatives to the nonrenewable and high-polluting fossil fuels. Photocatalysis, photoelectrocatalysis, and electrocatalysis provide promising avenues for sustainable energy conversion. Single- and dual-component catalytic systems based on nanomaterials have been intensively studied for decades, but their intrinsic weaknesses hamper their practical applications. Multicomponent nanomaterial-based systems, consisting of three or more components with at least one component in the nanoscale, have recently emerged. The multiple components are integrated together to create synergistic effects and hence overcome the limitation for outperformance. Such higher-efficiency systems based on nanomaterials will potentially bring an additional benefit in balance-of-system costs if they exclude the use of noble metals, considering the expense and sustainability. It is therefore timely to review the research in this field, providing guidance in the development of noble-metal-free multicomponent nanointegration for sustainable energy conversion. In this work, we first recall the fundamentals of catalysis by nanomaterials, multicomponent nanointegration, and reactor configuration for water splitting, CO2 reduction, and N2 reduction. We then systematically review and discuss recent advances in multicomponent-based photocatalytic, photoelectrochemical, and electrochemical systems based on nanomaterials. On the basis of these systems, we further laterally evaluate different multicomponent integration strategies and highlight their impacts on catalytic activity, performance stability, and product selectivity. Finally, we provide conclusions and future prospects for multicomponent nanointegration. This work offers comprehensive insights into the development of cost-competitive multicomponent nanomaterial-based systems for sustainable energy-conversion technologies and assists researchers working toward addressing the global challenges in energy and the environment.

Baseline immunity and impact of chemotherapy on immune microenvironment in cervical cancer.

BACKGROUND: We aimed to comprehensively evaluate the immunologic landscape at baseline and upon chemotherapy in cervical cancer. The information should aid ongoing clinical investigations of checkpoint blockade immunotherapies in this disease setting. METHODS: A series of 109 cervical carcinoma patients was retrospectively assayed before and after neoadjuvant chemotherapy. Tumour-infiltrating immune markers (CD3, CD4, CD8, CD20, CD56, CD68, PD-1, PD-L1) were assessed by immunohistochemistry. RNA sequencing analysis was performed on matched pre- and post-treatment fresh-frozen tissues. RESULTS: At diagnosis, diverse immune cell types including CD20+ B cells, CD3+ T cells, CD56+ natural killer (NK) cells, and CD68+ macrophages were detected in different proportions of cervical carcinoma. Unsupervised hierarchical clustering evidently showed that CD4+ and CD8+ T cell abundance correlated with PD-L1 expression. Based on the immune infiltration patterns, the patients could be stratified into four groups with prognostic relevance, namely, 'immuno-active', 'immuno-medial', 'immuno-NK', and 'immuno-deficient'. Neoadjuvant chemotherapy was associated with increased CD4, CD8, CD20, and CD56 signals, most prominently in good responders. Transcriptomic data corroborated the improved anticancer immunity and identified immunosuppressive CD200 upregulation following chemotherapeutic intervention. CONCLUSIONS: A subset of cervical cancer harbours active immune microenvironment, and chemotherapy treatment may further exert locoregional immunostimulation. Immune checkpoint inhibitors as combination or maintenance therapies warrant future exploration in clinic.

Identification of potential key genes and key pathways related to clear cell renal cell carcinoma through bioinformatics analysis.

Clear cell renal cell carcinoma (ccRCC) is a common malignancy of the genitourinary system and is associated with high mortality rates. However, the molecular mechanism of ccRCC pathogenesis is still unclear, which translates to few effective diagnostic and prognostic biomarkers. In this study, we conducted a bioinformatics analysis on three Gene Expression Omnibus datasets and identified 437 differentially expressed genes (DEGs) related to ccRCC development and prognosis, of which 311 and 126 genes are respectively down-regulated and up-regulated. The protein-protein interaction network of these DEGs consists of 395 nodes and 1872 interactions and 2 prominent modules. The Staphylococcus aureus infection and complement and coagulation cascades are significantly enriched in module 1 and are likely involved in ccRCC progression. Forty-two hub genes were screened, of which von Willebrand factor, TIMP metallopeptidase inhibitor 1, plasminogen, formimidoyltransferase cyclodeaminase, solute carrier family 34 member 1, hydroxyacid oxidase 2, alanine-glyoxylate aminotransferase 2, phosphoenolpyruvate carboxykinase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2 are possibly related to the prognosis of ccRCC. The differential expression of all nine genes was confirmed by quantitative real-time polymerase chain reaction analysis of the ccRCC and normal renal tissues. These key genes are potential biomarkers for the diagnosis and prognosis of ccRCC and warrant further investigation.

The use of mixed-metal single source precursors for the synthesis of complex metal oxides.

Complex metal oxides, defined as metal oxide materials with multiple metals, phases or including dopants, are used in a huge variety of modern applications ranging from photocatalysis, transparent conductive materials, supercapacitors and battery components. In this feature article, the use of mixed-metal single source precursors to synthesise complex metal oxides is explored. The structures and decomposition/reaction pathways of various precursors including mixed-metal alkoxides, complexes with chelating ligands, clusters, polyoxometallates, and metal-organic frameworks are discussed. The advantages and opportunities of using a single source precursor strategy are investigated and highlighted.

A simple one-step synthetic route to access a range of metal-doped polyoxovanadate clusters.

VO(OiPr)3 is a useful precursor for the synthesis of a range of metal-doped polyoxovanadate (POV) cage compounds, its reactions with hydrated metal salts providing a route to arrangements containing Bi and other main group metals, transition metals and lanthanides. The new POV compounds [Bi2(DMSO)6V12O33Br]2[M(DMSO)6] (2Br-M, M = CoII, NiII, CuII, ZnII) [Bi2(DMSO)6V12O33Cl]2[Ca(DMSO)x]·yDMSO (2Cl-Ca), [Bi2(DMSO)6V12O33Cl]2[LnCl(DMSO)7] (2Cl-Ln, Ln = LaIII, CeIII, EuIII), [Bi2(DMSO)6V10O28F2]3[Bi(DMSO)5]2 (3), [V12O32(DMSO)][Gd(NO3)(DMSO)5.5]2 (4) and [Ln(DMSO)4V12O32Cl][LnCl(DMSO)7] (5Cl-Ln, Ln = CeIII, EuIII) have been structurally characterised, and their properties studied using UV-Vis spectroscopy and cyclic voltammetry. Drop-casting these compounds onto fluorine-doped tin oxide followed by calcination provides a simple approach to thin films of metal-doped BiVO4 or LnVO4, depending on the composition of the cage precursor. The applications of the BiVO4 films as photoanodes for water oxidation is explored, with transition metal doping of BiVO4 improving the activity (∼1.8-2.4 times the photocurrent density of undoped BiVO4 at 1.23 V vs. RHE) while lanthanide or Ca-doping is detrimental.

Clinicopathological, microenvironmental and genetic determinants of molecular subtypes in KEAP1/NRF2-mutant lung cancer.

Somatic KEAP1-NRF2 pathway alterations are frequently detected in both lung adenocarcinomas and squamous cell carcinomas. However, the biological characteristics and molecular subtypes of KEAP1/NRF2-mutant lung cancer remain largely undefined. Here, we performed a stepwise, integrative analytic and experimental interrogation of primary tumors and cancer cell lines harboring KEAP1 or NFE2L2 (encoding NRF2) gene mutations. First, we discovered that KEAP1/NRF2-mutant lung cancer presented APOBEC-mediated mutational signatures, impaired tumor angiogenesis, elevated hypoxic stress and deficient immune-cell infiltrates. Second, gene expression-based subtyping revealed three molecular subsets of KEAP1/NRF2-mutant lung adenocarcinomas and two molecular subsets of KEAP1/NRF2-mutant lung squamous cell carcinomas, each associated with distinguishing genetic, differentiation, immunological and clinicopathological properties. Third, single-sample prediction allowed for de novo identification of KEAP1/NRF2-active tumors within KEAP1/NRF2-wild-type samples. Our data demonstrate that KEAP1/NRF2-mutant lung cancer is a microenvironmentally distinct, biologically heterogeneous, and clinically underestimated disease. These new pathological and molecular insights may accelerate the development of efficacious therapeutic strategies against human malignancies featured by KEAP1-NRF2 pathway activation.

Single-Source Bismuth (Transition Metal) Polyoxovanadate Precursors for the Scalable Synthesis of Doped BiVO4 Photoanodes.

Single-source precursors are used to produce nanostructured BiVO4 photoanodes for water oxidation in a straightforward and scalable drop-casting synthetic process. Polyoxometallate precursors, which contain both Bi and V, are produced in a one-step reaction from commercially available starting materials. Simple annealing of the molecular precursor produces nanocrystalline BiVO4 films. The precursor can be designed to incorporate a third metal (Co, Ni, Cu, or Zn), enabling the direct formation of doped BiVO4 films. In particular, the Co- and Zn-doped photoanodes show promise for photoelectrochemical water oxidation, with photocurrent densities >1 mA cm-2 at 1.23 V vs reversible hydrogen electrode (RHE). Using this simple synthetic process, a 300 cm2 Co-BiVO4 photoanode is produced, which generates a photocurrent of up to 67 mA at 1.23 V vs RHE and demonstrates the scalability of this approach.