Itaconate transporter SLC13A3 confers immunotherapy resistance via alkylation-mediated stabilization of PD-L1.

Itaconate is a metabolite catalyzed by cis-aconitate decarboxylase (ACOD1), which is mainly produced by activated macrophages and secreted into the extracellular environment to exert complex bioactivity. In the tumor microenvironment, itaconate is concentrated and induces an immunosuppressive response. However, whether itaconate can be taken up by tumor cells and its mechanism of action remain largely unclear.

CDC20-Mediated Selective Autophagy Degradation of PBRM1 Affects Immunotherapy for Renal Cell Carcinoma.

Polybromo 1 (PBRM1) inactivating mutations are associated with clinical benefit from immune checkpoint inhibitor treatments in clear cell renal cell carcinoma (ccRCC). However, whether targeting PBRM1 has the potential to enhance immunotherapy efficacy in patients with wild-type PBRM1 and the upstream pathways that regulate PBRM1 protein stability remain unclear. Here, it is demonstrated that PBRM1 knockdown induced M1 macrophage polarization and infiltration, which enhanced the efficacy of anti-PD-1 immunotherapy in RCC.

The Tumor Suppressor TPD52-Governed Endoplasmic Reticulum Stress is Modulated by APC.

Aberrant regulation of unfolded protein response (UPR)/endoplasmic reticulum (ER) stress pathway is associated with cancer development, metastasis, and relapse, and the UPR signal transducer ATF6 has been proposed as a diagnostic and prognostic marker for many cancers. However, a causal molecular link between ATF6 activation and carcinogenesis is not established. Here, it is found that tumor protein D52 (TPD52) integrates ER stress and UPR signaling with the chaperone machinery by promoting S2P-mediated cleavage of ATF6.

Photoinduced Co/Ni-cocatalyzed Markovnikov hydroarylation of unactivated olefins with aryl bromides.

Transition-metal-catalyzed hydroarylation of unactivated alkenes metal hydride hydrogen atom transfer (MHAT) is an attractive approach for the construction of C(sp)-C(sp) bonds. However, this kind of reaction focuses mainly on using reductive hydrosilane as a hydrogen donor. Here, a novel photoinduced Co/Ni-cocatalyzed Markovnikov hydroarylation of unactivated alkenes with aryl bromides using protons as a hydrogen source has been developed.

Photoredox-Catalyzed Amino-Radical-Transfer-Mediated Three-Component Alkylarylation of Alkenes.

We herein reported a novel photoredox-catalyzed three-component alkylarylation of vinyl arenes with alkylboronic pinacol esters (APEs) and cyanoarenes via radical addition/cross-coupling to construct 1,1-diarylalkanes. In this transformation, alkyl radicals were easily available by visible-light-induced oxidative N-H cleavage of morpholine, which used APEs as a radical precursor. Furthermore, this protocol exhibited a broad substrate scope, enabling various styrenes, APEs, and cyanoarenes, as well as bioactive molecule derivatives.

Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study).

Background: Video-assisted thoracoscopic (VATS) lobectomy can affect patients' pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation.

Targeting LYPLAL1-mediated cGAS depalmitoylation enhances the response to anti-tumor immunotherapy.

Cyclic GMP-AMP synthase (cGAS) binds pathogenic and other cytoplasmic double-stranded DNA (dsDNA) to catalyze the synthesis of cyclic GMP-AMP (cGAMP), which serves as the secondary messenger to activate the STING pathway and innate immune responses. Emerging evidence suggests that activation of the cGAS pathway is crucial for anti-tumor immunity; however, no effective intervention method targeting cGAS is currently available. Here we report that cGAS is palmitoylated by ZDHHC9 at cysteines 404/405, which promotes the dimerization and activation of cGAS.

AhR diminishes the efficacy of chemotherapy via suppressing STING dependent type-I interferon in bladder cancer.

The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway.

Differential Alterations in Topology Property of Resting State Networks Associated With Mental Health and Childhood Trauma.

Context: Childhood trauma can lead to greater vulnerability to psychopathology and can affect person's mental health throughout his or her life cycle. Research on the associations between childhood trauma and developmental outcomes is critical to creating effective interventions.

Objective: The study intended to identify brain networks that are susceptible to childhood trauma by comparing differences in the networks of individuals with and without trauma, to investigate how changes in networks can mediate the effects childhood adversity on mental health.

Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins.

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity.

Osimertinib as neoadjuvant therapy in patients with EGFR-mutant resectable stage II-IIIB lung adenocarcinoma (NEOS): A multicenter, single-arm, open-label phase 2b trial.

Objectives: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been approved for EGFR-mutant non-small-cell lung cancer (NSCLC). We aimed to evaluate the efficacy and safety of neoadjuvant osimertinib in patients with EGFR-mutant resectable locally advanced NSCLC.

Materials And Methods: This single-arm, phase 2b trial (ChiCTR1800016948) was conducted at six centers in mainland China.

β-Ionone represses renal cell carcinoma progression through activating LKB1/AMPK-triggered autophagy.

β-Ionone, the end ring analog of β-carotenoids, has been proven to have an antitumor effect in a variety of cancers. In this study, we investigated the impact of β-ionone on renal cell carcinoma (RCC) cell lines (786-O and ACHN) using colony formation assays, flow cytometry analysis, and western blot analysis. We found that β-ionone effectively inhibited the proliferation of RCC cells in vitro, which was also confirmed in a xenograft model.

deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways.

Visible-Light-Driven [3 + 2]/[4 + 2] Annulation Reactions of Alkenes with -Aminopyridinium Salts.

The annulation reactions of benzoamidyl radicals with alkenes were realized under visible light irradiation with -Ir(ppy) as catalyst and -aminopyridinium salts as benzoamidyl radical precursors. The reaction can deliver two distinct types of products: in the case of vinyl arenes, [3 + 2] annulation product dihydrooxazoles were yielded exclusively; when alkyl-substituted alkenes were used, on the other hand, it afforded [4 + 2] annulation product dihydroisoquinolinones. Factors determining the reaction consequence were elucidated by DFT calculations.

Site-selective coupling of remote C(sp)-H/-C(sp)-H bonds enabled by Ru/photoredox dual catalysis and mechanistic studies.

Construction of C(sp)-C(sp) bonds regioselective coupling of C(sp)-H/C(sp)-H bonds is challenging due to the low reactivity and regioselectivity of C-H bonds. Here, a novel photoinduced Ru/photocatalyst-cocatalyzed regioselective cross-dehydrogenative coupling of dual remote C-H bonds, including inert γ-C(sp)-H bonds in amides and -C(sp)-H bonds in arenes, to construct -alkylated arenes has been accomplished. This metallaphotoredox-enabled site-selective coupling between remote inert C(sp)-H bonds and -C(sp)-H bonds is characterized by its unique site-selectivity, redox-neutral conditions, broad substrate scope and wide use of late-stage functionalization of bioactive molecules.

Multi-input adaptive neural network for automatic detection of cervical vertebral landmarks on X-rays.

Cervical vertebral landmark detection is a significant pre-task for vertebral relative motion parameter measurement, which is helpful for doctors to diagnose cervical spine diseases. Accurate cervical vertebral landmark detection could provide reliable motion parameter measurement results. However, different cervical spines in X-rays with various poses and angles have imposed quite challenges.

Ion-Specific Effects on Vesicle-to-Micelle Transitions of an Amino Acid Surfactant Probed by Chemical Trapping.

Ion-specific effects widely exist in biological and chemical systems and cannot be explained by classical theories. The complexity of ion-specific effects in protein systems at the molecular level necessitates the use of mimetic models involving smaller molecules, such as amino acids, oligopeptides, and other organic molecules bearing amide bonds. Therefore, it is of theoretical value to determine the effect of additional salts on the aggregation transitions of acyl amino acid surfactants.

Three-Component Ru-Catalyzed Regioselective Alkylarylation of Vinylarenes via -Selective C(sp)-H Bond Functionalization.

We report a novel Ru-catalyzed regioselective alkylarylation of vinylarenes with alkyl halides and arenes via -C(sp)-H bond functionalization to construct 1,1-diarylalkanes that generally show bioactivity. In this transformation, a wide spectrum of primary, secondary, and tertiary alkyl halides and electronically varied arenes was well-tolerated. This reaction is characterized by its exquisite regioselectivity of vinylarenes, unique -C(sp)-H selectivity, and redox-neutral conditions.

Intermittent chest tube clamping decreases chest tube duration time and drainage volume after lung cancer surgery in patients without air leak: an open-label, randomized controlled trial.

Background: Our previous retrospective study proved the safety and effectiveness of chest tube clamping in terms of shortening chest tube duration. However, it needed to be verified by a prospective study. This study sought to determine if intermittent chest tube clamping decreases chest tube duration and total drainage volume after lung cancer surgery in patients without air leak.

Feasibility study of hallux valgus measurement with a deep convolutional neural network based on landmark detection.

Objective: To develop a deep learning algorithm based on automatic detection of landmarks that can be used to automatically calculate forefoot imaging parameters from radiographs and test its performance.

Materials And Methods: A total of 1023 weight-bearing dorsoplantar (DP) radiographs were included. A total of 776 radiographs were used for training and verification of the model, and 247 radiographs were used for testing the performance of the model.

Photoredox-catalyzed redox-neutral difluoroalkylation to construct perfluoroketones with difluoroenoxysilanes.

A mild and facile approach to construct various perfluoroketones photo-catalyzed difluoroalkylation of difluoroenoxysilanes is developed. The reaction includes a strategy of combination of two fluorine-containing functional groups, which confers the reaction with characteristics like high efficiency, mild conditions, and broad scope. A variety of fluoroalkyl halides including perfluoroalkyl iodides, bromo difluoro esters and amides can be employed as radical precursors.

Inflammatory factor-based prognostic risk stratification for patients with metastatic castration-resistant prostate cancer treated with docetaxel.

To develop a simple inflammatory factor-based prognostic risk stratification system for patients with metastatic castration-resistant prostate cancer (mCRPC) receiving docetaxel as the initial treatment, we reviewed the data of 399 consecutive patients who received first-line docetaxel chemotherapy between January 2013 and June 2019 retrospectively. The optimal cut-off values for the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in terms of survival were calculated by ROC curves. Patients were stratified into favourable (lower NLR and lower PLR), intermediate (higher NLR and lower PLR, or lower NLR and higher PLR) and poor (higher NLR and higher PLR) groups.

Cu-Catalyzed Direct C-H Alkylation of Polyfluoroarenes via Remote C(sp)-H Functionalization in Carboxamides.

A novel dehydrogenative coupling reaction of -fluorocarboxamides with polyfluoroarenes forming C(sp)-C(sp) bonds enabled by copper catalysis has been accomplished. -Fluorocarboxamides are postulated to undergo copper-mediated dehydrogenative cross-coupling reaction with electron-deficient polyfluoroarenes via a radical pathway. Benzylic C-H bonds and aliphatic C-H bonds in -fluorocarboxamides could proceed smoothly and demonstrated excellent regioselectivity.