The lung immune prognostic index stratifies the occurrence of checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients: a multi-institutional cohort study.

Background: Lung immune prognostic index (LIPI) is associated with survival outcomes in patients with non-small cell lung cancer (NSCLC) receiving immunotherapy, but the association with the occurrence of checkpoint inhibitor pneumonitis (CIP) is unclear.

Methods: We retrospectively included 1824 patients with advanced NSCLC who received immune checkpoint inhibitors (ICIs) at two institutions. Cox regression analysis and cumulative incidence curve were used to evaluate the predictive value of LIPI.

Zn/HO-mediated tandem reductive cyclization of 2-(2-nitrophenyl)-1-benzo[]imidazoles with aldehydes to synthesize 5,6-dihydrobenzo[4,5]imidazo[1,2-]quinazolines.

A one-pot tandem approach to synthesize 5,6-dihydrobenzo[4,5]imidazo[1,2-]quinolones has been developed from 2-(2-nitrophenyl)-1-benzo[]imidazoles and aldehydes a Zn/HO-mediated reductive cyclization process, characterised by cheap and readily available raw materials, a simple, green, economical and efficient protocol, good product yields and product diversity.

Photocatalyzed Three-Component Difluoroalkyl-Halogenation of Electron-Deficient Alkenes via a Halogen α-Nucleophilic Addition.

Here, we disclose a halogen α-nucleophilic addition via photocatalytic oxidation of the in-situ generated α-carbonyl radical of amides or esters to corresponding α-carbonyl cation. The α-carbon radical is generated by the β-addition of difluoroalkyl radical, formed by the photocatalytic reduction of BrCFCOR, to the α,β-unsaturated amides/esters. This umpolung strategy enables an efficient three-component difluoroalkyl-halogenation of α,β-unsaturated amides or esters with BrCFCOR and Cl/F-nucleophiles to produce diverse biologically important CF-containing α-halo-1,5-dicarboxylic derivatives under mild conditions.

Inverse conjugate additions of acrylic amides and esters with F/Cl/O/N-nucleophiles and CF reagents.

The conjugate additions of nucleophiles to conjugate acceptors are among the most powerful hetero-carbon bond formation reactions. The conjugate addition normally occurs via a β-nucleophilic addition, resulting in the formation of a stabilized α-carbanion intermediate that can be subsequently quenched by electrophiles or protons. Nevertheless, the inverse conjugate addition involving an α-specific nucleophilic addition remains less explored because of the electronic mismatch.

A minimally invasive technique for correcting extra-articular malunions of metacarpal fractures.

Purpose: This study aimed to assess the efficiency of a minimally invasive technique for correcting malunions of extra-articular metacarpal fractures, followed by percutaneous fixation using a cemented K-wire frame.

Methods: From January 2018 to January 2022, 31 patients (31 malunions of extra-articular metacarpal fractures) were treated. The mean age of the patients was 32 years (range, 21-52 years).

Antagonistic interaction between miR-143 and KRAS gene regulating male mouse germ cell apoptosis.

Precisely regulated spermatocyte growth, differentiation, and apoptosis are crucial for sustainable male fertility. miR-143 has been demonstrated to regulate gene expression and cell apoptosis in various human cancers. However, the function of mmu-mir-143 (miR-143) in mammalian testes and its underlying mechanism remains unexplored.

Hypochlorous Acid-Activatable NIR Fluorescence/Photoacoustic Dual-Modal Probe with High Signal-to-Background Ratios for Imaging of Liver Injury and Plasma Diagnosis of Sepsis.

Hypochlorous acid can be employed as a biomarker for blood infection (such as sepsis) and tissue damage (such as drug-induced liver injury, DILI), and the diagnosis of tissue damage or blood infection can be achieved through the detection of hypochlorous acid in relevant biological samples. Considering the complex environment and the diverse interferences in living organisms and blood plasma, developing new detection methods for HClO with high signal-to-background ratios is particularly important, and it can improve the accuracy of detection and quality of imaging based on a higher contrast, which makes the detection of HClO clearer and more accurate. Here, based on the advantages of the NIR fluorescence/photoacoustic dual-modal probe, we reported a hypochlorous acid-activatable NIR fluorescence/photoacoustic dual-modal probe (NIRF-PA-HClO) based on the spirolactam ring-opening strategy in this paper.

Catalytic System-Controlled Regioselective 1,2- and 1,4-Carboannulations of [60]Fullerene.

Selective functionalization of fullerenes is an important but challenging topic in fullerene chemistry and synthetic chemistry. Here we present the first example of catalytic system-controlled regioselective 1,2- and 1,4-addition reactions for the flexible and efficient synthesis of novel 1,2- and 1,4-carbocycle-fused fullerenes via a palladium-catalyzed decarboxylative carboannulation process.

Pd(II)-catalyzed cascade annulation of -substituted anilines with CO, NHOAc and aldehydes to 1-substituted 2,3-dihydroquinazolin-4(1)-ones.

A facile and direct approach to 1-substituted 2,3-dihydroquinazolin-4(1)-ones has been developed Pd(II)-catalyzed one-pot cascade annulation of -substituted anilines with CO, NHOAc and aldehydes, and it features an intrinsic directing strategy, cheap and easily obtainable raw materials, low cost, high step economy and efficiency, broad substrate scope and good product diversity. This protocol has been successfully applied to the synthesis of glycozolone A and gram-level experiments. Based on the control experiments and the literature, the reaction mechanism was proposed.

Nickel-Catalyzed Deaminative Alkyl-Alkyl Cross-Coupling of Katritzky Salts with Cyclopropanols: Merging C-N and C-C Bond Activation.

Herein, we report a general and practical nickel-catalyzed deaminative alkylation of Katritzky salts with cyclopropyl alcohols via merging C-N and C-C bond activation. This protocol enables the formation of an alkyl-alkyl bond along with the generation of a versatile ketone functional group in a single operation, thus providing a convenient approach for accessing β-alkyl ketones. This reaction is distinguished by its high functional group tolerance, broad substrate scope, and efficient late-stage derivatization of complex bioactive molecules.

Aerobic Oxidative Hydroxylation of Arylboronic Acids under Visible-Light Irradiation without Metal Catalysts or Additives.

Phenols are versatile synthetic intermediates and key structural motifs in many natural products and biologically active compounds. We herein report a visible-light-induced aerobic oxidative hydroxylation of arylboronic acids/pinacol esters using air as oxidant and without using any catalysts and base, etc., additives, providing a green entry to a variety of phenols in a highly efficient and concise fashion.

Interrupted N-Heterocyclic Carbene-Catalyzed Radical Coupling Strategy: A Versatile Platform for Alkylation and Arylation of [60]Fullerene.

An interrupted N-heterocyclic carbene-catalyzed radical coupling strategy is disclosed for efficient alkylation and arylation of [60]fullerene. This novel and general strategy bridges the gap between organocatalytic radical cross-coupling and functionalization of fullerenes. Readily available feedstocks, remarkably broad substrate scope and functional group compatibility, and convenient late-stage nanomodification of complex molecules make this strategy with incomparable diversity and practicality in the synthesis of monoalkylated and -arylated fullerenes.

An asymmetrical flavylium based probe with large Stokes shift and near infrared emission for highly sensitive detecting and visualizing cellular drug induced HS fluctuations.

Hydrogen sulfide (HS) has been recognized as an important gaseous signaling molecule in living systems, and is of great significance in many pathological and physiological processes. Misregulation of endogenous HS is implicated in various diseases in the neuronal, gastrointestinal, circulatory, and endocrine systems. Fluorescent probe with large Stokes shift and near infrared emission, is ideal candidate for imaging applications to prevent excitation scattering, autofluorescence interference, matrix absorption caused signal loss, and sample destruction.

Equivalent Response Strategy for Sensing Total Biothiols in Human Serums and Living Cells Using a Hemicyanine-Based Self-Immolative Probe.

Biothiols including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) are crucial in maintaining the redox balance in the body, and the metabolism and transportation of biothiols rely on the coreaction of diverse proteins and enzymes. The abnormal concentrations and metabolism of biothiols are closely associated with many diseases. However, due to the same active reaction site of the sulfydryl group in biothiols, it is inevitable to bear a confused signal of mutual influence on both nonselective detection and discriminate detection, which presents a serious challenge of accurately sensing or imaging the three biothiols.

Co-, N-doped carbon dot nanozymes based on an untriggered ROS generation approach for anti-biofilm activities and anti-bacterial treatment.

Bacterial infections originating from food, water, and soil are widely recognized as significant global public health concerns. Biofilms are implicated in approximately two-thirds of bacterial infections. In recent times, nanomaterials have emerged as potential agents for combating biofilms and bacteria, with many of them being activated by light and HO to generate reactive oxygen species (ROS).

Cope Rearrangement of 1-Acyl-2-vinylcyclopropanes to Cyclohept-4-Enones.

Cycloheptenones are widespread in natural products and bioactive molecules. An efficient and convenient NaH-mediated Cope Rearrangement of doubly activated vinylcyclopropanes is reported for the synthesis of cyclohepten-4-ones. These flexible intramolecular reactions were applicable to a wide range of substrates and could be performed on gram scale.

Arterial Spin Labeling and Amide Proton Transfer Imaging can Differentiate Glioblastoma from Brain Metastasis: A Systematic Review and Meta-Analysis.

Background: Currently, arterial spin labeling (ASL) and amide proton transfer (APT) imaging have shown potential for distinguishing glioblastoma from brain metastases. Thus, a meta-analysis was conducted to investigate this further.

Methods: An extensive and comprehensive search was conducted in 6 English and Chinese databases according to predefined inclusion and exclusion criteria, encompassing data up to July 2023.

Protective effects of puerarin on liver tissue in Salmonella-infected chicks: a proteomic analysis.

Salmonella enterica is a zoonotic bacterium that not only causes serious economic losses to the livestock and poultry industries but also seriously endangers human health. Long-term indiscriminate use of antibiotics has led to drug resistance in Salmonella, and thus the identification of alternatives to antibiotics is crucial. In this study, the effects of puerarin on the S.

A novel self-assembled nucleobase-nanofiber platform of CDN to activate the STING pathway for synergistic cancer immunotherapy.

2', 3'-cGAMP (CDN) as cGAS-STING pathway agonist is extensively used in tumor treatment. However, due to its negatively charged nature (containing two phosphate groups) and high hydrophilicity, CDN faces challenges in crossing cell membranes, resulting in reduced efficiency of its use. Additionally, CDN is susceptible to inactivation through phosphodiesterase hydrolysis.

Thermo-activated periodate oxidation process for tetracycline degradation: Kinetics and byproducts transformation pathways.

Periodate-based advanced oxidation processes have been diffusely practiced for pollutant decontamination. However, the thermo-activation of periodate process (heat/PI), an effective water pollution removal process, has been rarely discussed, and the degradation pathway of this heat/PI system requires investigation. In this work, tetracycline antibiotics were selected as the model micropollutant for the comprehensive evaluation of the heat/PI system.

Dearomative Ring-Fused Azafulleroids and Carbazole-Derived Metallofullerenes: Reactivity Dictated by Encapsulation in a Fullerene Cage.

Herein, we report divergent additions of 2,2'-diazidobiphenyls to C and Sc N@I -C . In stark contrast to that of the previously reported bis-azide additions, the unexpected cascade reaction leads to the dearomative formation of azafulleroids 2 fused with a 7-6-5-membered ring system in the case of C . In contrast, the corresponding reaction with Sc N@I -C switches to the C-H insertion pathway, thereby resulting in multiple isomers, including a carbazole-derived [6,6]-azametallofulleroid 3 and a [5,6]-azametallofulleroid 4 and an unusual 1,2,3,6-tetrahydropyrrolo[3,2-c]carbazole-derived metallofullerene 5, whose molecular structures have been unambiguously determined by single-crystal X-ray diffraction analyses.

Remodeling of Tumor Microenvironment by Nanozyme Combined cGAS-STING Signaling Pathway Agonist for Enhancing Cancer Immunotherapy.

Nanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME by producing reactive oxygen species (ROS), which lead to positive oxidative stress in tumor cells. Cyclic dinucleotide (2',3'-cGAMP), as a second messenger, exists in the TME and can regulate it to achieve antitumor activity.

Palladium-catalyzed intramolecular aza-Wacker-type cyclization of vinyl cyclopropanecarboxamides to access conformationally restricted aza[3.1.0]bicycles.

A palladium(ii)-catalyzed intramolecular oxidative aza-Wacker-type reaction of vinyl cyclopropanecarboxamides to access a series of conformationally restricted highly substituted aza[3.1.0]bicycles is reported.