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Highlights Increased use of primary tumor resection plus metastasectomy benefited patients with left-sided tumors but not those with right-sided tumors. Increased use of primary tumor resection alone did not improve survival in either left or right-sided tumor group. Overuse of palliative primary tumor resection should be avoided.

There is a lack of high-quality, large-scale, real-world evidence from patients with metastatic colorectal cancer (mCRC), especially in China. It remains unclear whether efforts to improve the quality of care for mCRC would improve patient survival outcomes in real-world practice. On the basis of an intelligent big-data platform, we established a large-scale retrospective cohort of mCRC patients. We investigated the temporal changes in the systemic and local treatment (resection, ablation, or radiation to liver, lung, or extrahepatic and/or extrapulmonary metastases) patterns of mCRC, and whether these changes were associated with improved overall survival (OS) over time. Between July 2012 and December 2018, 3403 eligible patients were included in this research. The median OS was 42.8 months (95% confidence interval (CI), 40.7–46.6) for the entire cohort, 25.6 months (95% CI, 24.7–26.9) for those treated with systemic therapy only, and not reached (95% CI, 78.6 months–not reached) for those receiving local therapy. The utility rate of local therapy increased continuously from 37.9% in 2012–2014 to 46.9% in 2017–2018. A dramatic increase in the utility rate of either cetuximab or bevacizumab was observed since 2017 (39.9%, 43.2%, and 60.3% in 2012–2014, 2015–2016, and 2017–2018, respectively). Compared with 2012–2014, the OS of the entire population significantly improved in 2015–2016 (hazard ratio (HR) = 0.87 (95% CI, 0.78–0.99); P = 0.034), but not for patients receiving systemic therapy only (HR = 0.99 (95% CI, 0.86–1.14); P = 0.889), whereas an improved OS was found in 2015–2018 for both the entire population (HR = 0.75 (95% CI, 0.70–0.81); P

Abstract Background A critical and challenging process in immunotherapy is to identify cancer patients who could benefit from immune checkpoint inhibitors (ICIs). Exploration of predictive biomarkers could help to maximize the clinical benefits. Eph receptors have been shown to play essential roles in tumor immunity. However, the association between EPH gene mutation and ICI response is lacking. Methods Clinical data and whole-exome sequencing (WES) data from published studies were collected and consolidated as a discovery cohort to analyze the association between EPH gene mutation and efficacy of ICI therapy. Another independent cohort from Memorial Sloan Kettering Cancer Center (MSKCC) was adopted to validate our findings. The Cancer Genome Atlas (TCGA) cohort was used to perform anti-tumor immunity and pathway enrichment analysis. Results Among fourteen EPH genes, EPHA7-mutant (EPHA7-MUT) was enriched in patients responding to ICI therapy (FDR adjusted P

Background Progression-free survival (PFS) exhibits suboptimal performance as the surrogate endpoint for overall survival (OS) in trials studying immune checkpoint inhibitors (ICIs). Here we propose a novel surrogate endpoint, modified PFS (mPFS), which omits the events of disease progression (but not deaths) within 3 months after randomization.Methods PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized trials studying ICIs in advanced solid tumors with available PFS and OS data up to May 2020. Individual patient-level data (IPD) for PFS and OS were reconstructed for eligible trials. A simulation-based algorithm was used to match the reconstructed, disconnected PFS and OS IPD, and 1000 independent simulated datasets of matched PFS-OS IPD were generated for each trial. mPFS durations and statuses were then measured for each of the matched PFS-OS IPD. Trial-level correlation between Cox HRs for PFS or mPFS and HRs for OS was assessed using Pearson correlation coefficient (rp) weighted by trial size; patient-level correlation between PFS or mPFS and OS was assessed using Spearman’s rank correlation coefficient (rs). Findings were further validated using the original IPD from two randomized ICI trials.Results Fifty-seven ICI trials totaling 29,429 participants were included. PFS HR showed moderate correlation with OS HR (rp=0.60), and PFS was moderately correlated with OS at the patient level (median rs=0.66; range, 0.65–0.68 among the 1000 simulations). In contrast, mPFS HR achieved stronger correlation with OS HR (median rp=0.81; range, 0.77–0.84), and mPFS was more strongly correlated with OS at the patient level (median rs=0.79; range, 0.78–0.80). The superiority of mPFS over PFS remained consistent in subgroup analyses by cancer type, therapeutic regimen, and treatment setting. In both trials with the original IPD where experimental treatment significantly improved OS, mPFS successfully captured such clinical benefits whereas PFS did not.Conclusions mPFS outperformed PFS as the surrogate endpoint for OS in ICI trials. mPFS is worthy of further investigation as a secondary endpoint in future ICI trials.

Ferroptosis is regulated by genes and participates in the physiological and pathological processes of ischemia-reperfusion injury, stroke, tumor and other diseases. The pathogenic mechanism is not yet clear. It is known that regulating p53 gene can induce ferroptosis of endothelial cells and tumor cells. Inhibiting ferroptosis enables GPX4 to function normally, blocking lipid oxidation on cell membranes, reducing the accumulation of reactive oxygen species (ROS), and protecting normal cells. In view of the polyreactivity of ferroptosis, it may help kill cancer cells and may damage normal cells. Therefore, genes related to regulatory ferroptosis sensitivity and the trigger mechanism need to be elucidated urgently. This article mainly reviews the known functional mechanisms of regulatory ferroptosis sensitive genes such as GPX4, FSP1, SLC7A11, P53, et al, in order to provide a reference for the in-depth analysis of ferroptosis research and the selection of drugs for major diseases. [ABSTRACT FROM AUTHOR]

Bioinspired transformation of small-molecules to energy-related feedstocks is an attractive research area to overcome both the environmental issues and the depletion of fossil fuels. The highly effective metalloenzymes in nature provide blueprints for the utilization of bioinspired metal complexes for artificial photosynthesis. Through simpler structural and functional mimics, the representative herein is the pivotal development of several critical small molecule conversions catalyzed by metal complexes, e.g., water oxidation, proton and CO2 reduction and organic chemical transformation of small molecules. Of great achievement is the establishment of bioinspired metal complexes as catalysts with high stability, specific selectivity and satisfactory efficiency to drive the multiple-electron and multiple-proton processes related to small molecule transformation. Also, potential opportunities and challenges for future development in these appealing areas are highlighted. [ABSTRACT FROM AUTHOR]

Photoelectrochemistry enables the formation of a variety of active intermediates for organic synthesis in an environmentally friendly manner. Herein, a photoelectrochemical cell is fabricated to realize activation of P–H/C–H bonds for cross-coupling hydrogen evolution. As compared with an electrochemical cell, nearly 90% external bias input is saved to drive the C–P bond construction with good to excellent yields. [ABSTRACT FROM AUTHOR]

CdS and CdS/ZnS colloidal nanocrystals (NCs) capped with inorganic sulfide (S2−) ligands were directly synthesized with no aid of organic ligands in water. The obtained CdS/ZnS-S2− NCs show a surprising activity for hydrogen evolution with a rate of 1.61 mmol mg−1 h−1 and an internal quantum yield of 54% under 465 nm light irradiation. [ABSTRACT FROM AUTHOR]

Abstract: Eosin Y, a well‐known economical alternative to metal catalysts in visible‐light‐driven single‐electron transfer‐based organic transformations, can behave as an effective direct hydrogen‐atom transfer catalyst for C−H activation. Using the alkylation of C−H bonds with electron‐deficient alkenes as a model study revealed an extremely broad substrate scope, enabling easy access to a variety of important synthons. This eosin Y‐based photocatalytic hydrogen‐atom transfer strategy is promising for diverse functionalization of a wide range of native C−H bonds in a green and sustainable manner. [ABSTRACT FROM AUTHOR]

Owing to promoted electron–hole separation, the catalytic activity of semiconducting quantum dots (QDs) towards solar hydrogen (H2) production has been significantly enhanced by forming self-assembled clusters with ZnSe QDs made ex situ. Taking advantage of the favored interparticle hole transfer to ZnSe QDs, the rate of solar H2 evolution of CdSe QDs can be increased to ∼30 000 μmol h−1 g−1 with ascorbic acid as the sacrificial reagent, ∼150-fold higher than that of bare CdSe QDs clusters under the same conditions. [ABSTRACT FROM AUTHOR]

Surface stoichiometry is a sensitive parameter affecting the decay dynamics of photogenerated hole–electron pairs of QDs. However, the effect of this manipulation on artificial photocatalytic H2 evolution is unclear. Here, we report that surface stoichiometry manipulation is a facile and feasible approach for enhancing H2 photogeneration of QDs. In the absence of an external cocatalyst, a decrease in the surface Se ratio of CdSe QDs from ∼16.7% to ∼4.9% gives a more than 10-fold increase in solar H2 evolution. Taking Ni(ii) as an external cocatalyst, CdSe QDs with a surface Se ratio of ∼4.9% can produce ∼1600 ± 151 μmol H2 gas during 27 h of visible-light irradiation, giving a total turnover number of (1.24 ± 0.12) × 105 on CdSe QDs and an apparent quantum yield of 10.1%, which is about 8 times that of CdSe QDs with a surface Se ratio of ∼16.7% under the same conditions. Mechanistic insights obtained by a combination of steady-state and time-resolved spectroscopic techniques indicate that surface stoichiometry exerts a significant influence on the exciton kinetics of CdSe QDs: a higher ratio of surface Se would increase the possibility of exciton recombination through hole trapping, thus depressing the performance of solar H2 evolution. [ABSTRACT FROM AUTHOR]

Abstract: The increasing demand for sustainable and environmentally benign energy has stimulated intense research to establish highly efficient photo‐electrochemical (PEC) cells for direct solar‐to‐fuel conversion via water splitting. Light absorption, as the initial step of the catalytic process, is regarded as the foundation of establishing highly efficient PEC systems. To make full use of visible light, sensitization on photoelectrodes using either molecular dyes or semiconducting quantum dots provides a promising method. In this field, however, there remain many fundamental issues to be solved, which need in‐depth study. Here, fundamental knowledge of PEC systems is introduced to enable readers a better understanding of this field. Then, the development history and current state in both molecular dye‐ and quantum dot‐sensitized photocathodes for PEC water splitting are discussed. A systematical comparison between the two systems has been made. Special emphasis is placed on the research of quantum dot‐sensitized photocathodes, which have shown superiority in both efficiency and durability towards PEC water splitting at the present stage. Finally, the opportunities and challenges in the future for sensitized PEC water‐splitting systems are proposed. [ABSTRACT FROM AUTHOR]

To achieve sustainable production of hydrogen (H2) through water splitting, establishing efficient and earth-abundant electrocatalysts is of great necessity. Morphology engineering of graphene is now shown to modulate the electronic structure of carbon skeleton and in turn endow it with excellent ability of proton reduction. Three-dimensional (3D) graphene networks with a high density of sharp edge sites are synthesized. Electrocatalytic measurements indicate that the obtained 3D graphene networks can electrocatalyze H2 evolution with an extremely low onset potential of about 18 mV in 0.5 m H2SO4 solution, together with good stability. A combination of control experiments and density functional theory (DFT) investigations indicates that the exceptional H2 evolution performance is attributed to the abundant sharp edge sites of the advanced frameworks, which are responsible for promoting the adsorption and reduction of protons. [ABSTRACT FROM AUTHOR]

Abstract: Photoelectrochemical (PEC) water splitting involving a sensitized photocathode has emerged as an extremely promising pathway for achieving solar‐to‐fuel conversion. Here it is reported that merely by modulating the morphology of hole‐transfer layer of NiO film to give a regular porous structure, the PEC performance of quantum dots (QDs) sensitized photocathodes can be dramatically enhanced. Mechanistic insights reveal that the porous structure not only increases the loading amount of QDs for enhanced light capture, but also facilitates the process of interfacial hole transfer and migration, which enable a 2.6‐fold enhancement of PEC performance to a photocurrent of ≈136 μA cm−2. The strategy introduced here provides an effective and facile pathway for further improving the efficiency of artificial photosynthesis. [ABSTRACT FROM AUTHOR]

Due to their enhanced light harvesting, favored interfacial charge transfer and excellent proton reduction activity, hybrid photocatalysts of metallic 1T-MoS2 nanosheets and inorganic-ligand stabilized CdSe/ZnS QDs obtained via a self-assembly approach can produce H2 gas with a rate of ∼155 ± 3.5 μmol h−1 mg−1 under visible-light irradiation (λ = 410 nm), the most exceptional performance of solar H2 evolution using MoS2 as a cocatalyst known to date. [ABSTRACT FROM AUTHOR]

Direct C-S bond coupling is an attractive way to construct aryl sulfur ether, a building block for a variety of biological active molecules. Herein, we disclose an effective model for regioselective thiolation of the aromatic C-H bond by thiol activation instead of arene activation. Strikingly, this method has been applied into anisole derivatives that are not available in the arene activation approach to forge a single thioether isomer with high reactivity.

As one of the most critical approaches to resolve the energy crisis and environmental concerns, carbon dioxide (CO 2 ) photoreduction into value-added chemicals and solar fuels (for example, CO, HCOOH, CH 3 OH, CH 4 ) has attracted more and more attention. In nature, photosynthetic organisms effectively convert CO 2 and H 2 O to carbohydrates and oxygen (O 2 ) using sunlight, which has inspired the development of low-cost, stable, and effective artificial photocatalysts for CO 2 photoreduction. Due to their low cost, facile synthesis, excellent light harvesting, multiple exciton generation, feasible charge-carrier regulation, and abundant surface sites, semiconductor quantum dots (QDs) have recently been identified as one of the most promising materials for establishing highly efficient artificial photosystems. Recent advances in CO 2 photoreduction using semiconductor QDs are highlighted. First, the unique photophysical and structural properties of semiconductor QDs, which enable their versatile applications in solar energy conversion, are analyzed. Recent applications of QDs in photocatalytic CO 2 reduction are then introduced in three categories: binary II-VI semiconductor QDs (e.g., CdSe, CdS, and ZnSe), ternary I-III-VI semiconductor QDs (e.g., CuInS 2 and CuAlS 2 ), and perovskite-type QDs (e.g., CsPbBr 3 , CH 3 NH 3 PbBr 3 , and Cs 2 AgBiBr 6 ). Finally, the challenges and prospects in solar CO 2 reduction with QDs in the future are discussed., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A trifluoroacetic acid-facilitated ortho amination of alkoxyl arene has been established via anodic oxidation in an undivided cell. In the absence of any additional metal or oxidant reagents, a series of aromatic and heteroaromatic amine derivatives have been synthesized in good to excellent yields. Our findings reveal the possibility of achieving complete ortho -selective amination of a simple arene, which emerges as an efficient route for facile and large-scale organic synthesis.

The catalytic ability of graphitic carbon nitride is greatly affected by its intrinsic electronic properties. Although combination with chromophore has been demonstrated to be one of the promising approaches to improve the catalytic performance of carbon nitride, it is imperative to understand the key factors governing the whole process. Here, we report a composite photocatalyst CN-P by embedding perylene unit into the matrix of carbon nitride. The composite photocatalyst could catalyze hydrogen evolution with a high rate of 17.7 mmol h -1 g -1 , which is 2.8 times faster than pure carbon nitride. The apparent quantum efficiency is high up to be 5.8% at 450 nm. Detailed studies reveal that the light absorption ability and charge separation efficiency are greatly enhanced in the synthesized catalyst. These are the key factors for the improved hydrogen evolution ability of CN-P than that of pure carbon nitride.

Colloidal quantum dots (QDs) have demonstrated great promise in artificial photosynthesis. However, the ultrasmall size hinders its controllable and effective interaction with cocatalysts. To improve the poor interparticle electronic communication between free QD and cocatalyst, we design here a self-assembled architecture of nanoparticles, QDs and Pt nanoparticles, simply jointed together by molecular polyacrylate to greatly enhance the rate and efficiency of interfacial electron transfer (ET). The enhanced interparticle electronic communication is confirmed by femtosecond transient absorption spectroscopy and X-ray transient absorption. Taking advantage of the enhanced interparticle ET with a time scale of ∼65 ps, 5.0 mL of assembled CdSe/CdS QDs/cocatalysts solution produces 94 ± 1.5 mL (4183 ± 67 μmol) of molecular H 2 in 8 h, giving rise to an internal quantum yield of ∼65% in the first 30 min and a total turnover number of >1.64 × 10 7 per Pt nanoparticle. This study demonstrates that self-assembly is a promising way to improve the sluggish kinetics of the interparticle ET process, which is the key step for advanced H 2 photosynthesis.

An earth-abundant, low-cost cobalt porphyrin complex (CoTCPP) is designed as a molecular catalyst to work on three-dimensional BiVO4 film electrode for water oxidation for the first time. Under illumination of a 100 mW cm(-2) Xe lamp, the CoTCPP-functionalized BiVO4 photoanode exhibits a 2-fold enhancement in photocurrent density at 1.23 V vs RHE and nearly a 450 mV cathodic shift at 0.5 mA cm(-2) photocurrent density relative to bare BiVO4 in 0.1 M Na2SO4 (pH = 6.8). Simultaneously, stoichiometric oxygen and hydrogen are generated with a faradic efficiency of 80% over 4 h. The activity and stability of the BiVO4 photoanode are dramatically increased by molecular CoTCPP, giving rise to higher performance than previously reported noble metal ruthenium complex-modified BiVO4 photoanode. By using hydrogen peroxide as the hole scavenger, we demonstrate that molecular CoTCPP catalyst greatly suppresses the hole-electron recombination on the surface of BiVO4 semiconductor, which offers a promising route toward high efficiency, low cost, practical solar fuel generation device.