Liver function dynamics in advanced hepatocellular carcinoma receiving immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization.

Background: The efficacy and safety of transarterial chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) have been established. However, it remains unclear whether the addition of TACE to systemic therapies exacerbates liver function deterioration and increases mortality risk.

Objectives: To assess liver function changes and their impact on prognosis in patients with advanced hepatocellular carcinoma (HCC) treated with ICIs and anti-VEGF antibody/TKIs with or without TACE as first-line therapy.

Dinuclear Dicationic Iridium Complexes for Highly Synergistic Photodynamic and Photothermal Therapy to Chemoresistant Cancer.

A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT and PTT) for cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen and superoxide anion, and release heat when exposed to infrared (IR) irradiation, thus inducing reactive oxygen species (ROS)-associated cell disruption and thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis.

Bithiophene-Functionalized Infrared Two-Photon Absorption Metal Complexes as Single-Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage.

In situ observation of a stepwise [2 + 2] photocycloaddition process using fluorescence spectroscopy.

Using highly sensitive and selective in situ techniques to investigate the dynamics of intermediates formation is key to better understand reaction mechanisms. However, investigating the early stages of solid-state reactions/transformations is still challenging. Here we introduce in situ fluorescence spectroscopy to observe the evolution of intermediates during a two-step [2 + 2] photocycloaddition process in a coordination polymer platform.

Bleeding the Excited State Energy to the Utmost: Single-Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low-Power Laser.

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation.

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy.

Photodynamic therapy (PDT) uses a combination of photosensitizers (PSs), light sources, and reactive oxygen species (ROS) to damage only the desired target and keep normal tissues from being hurt. The dark cytotoxicity (chemotoxicity) of PSs, leading to whole-body damage in the absence of irradiation, is a major limiting factor in PDT. How to simultaneously increase ROS generation and decrease dark cytotoxicity is an essential challenge that must be resolved in PS research.

Dinuclear osmium complexes as mitochondrion-targeting antitumor photothermal agents .

Four dinuclear osmium complexes have been constructed for antitumor phototherapy. The most potent Os4 has extremely high photothermal conversion capability under irradiation of an 808 nm low-power laser, targets mitochondria in human melanoma cells without nucleus affinity, and acts as an antitumor photothermal therapy agent and .

In vivo Realization of Dual Photodynamic and Photothermal Therapy for Melanoma by Mitochondria Targeting Dinuclear Ruthenium Complexes under Civil Infrared Low-power Laser.

A series of dinuclear Ru complexes with extremely high TPA cross sections in the range of 800-900 nm have been designed. The amphiphilic complex Ru3 containing tert-butyl groups has balanced performance in singlet oxygen generation and photothermal conversion and becomes the ideal drug candidate of the series. Ru3 targets mitochondria without penetrating the nucleus, which substantially increases its photodynamic therapy activity and reduces its dark cytotoxicity.

Polypyridyl ruthenium complexes as bifunctional TAR RNA binders and HIV-1 reverse transcriptase inhibitors.

Inhibitors of type 1 human immunodeficiency virus (HIV-1) reverse transcriptase are central to anti-HIV therapy. Most of their targets are enzymes, while very few could bind to viral RNA. Here we designed four new polypyridyl Ru(II) complexes, which could bind HIV-1 TAR RNA tightly and selectively by molecular recognition of hydrogen bonds, further stabilize the Ru(II)-RNA bound system by electrostatic attraction, and efficiently inhibit the Moloney murine leukemia virus (M-MuLV) and HIV-1 reverse transcriptase.

Controllable multiple-step configuration transformations in a thermal/photoinduced reaction.

Solid-state photochemical reactions of olefinic compounds have been demonstrated to represent powerful access to organic cyclic molecules with specific configurations. However, the precise control of the stereochemistry in these reactions remains challenging owing to complex and fleeting configuration transformations. Herein, we report a unique approach to control the regiospecific configurations of C = C groups and the intermediates by varying temperatures in multiple-step thermal/photoinduced reactions, thus successfully realizing reversible ring closing/opening changes using a single-crystal coordination polymer platform.

Tunable photosalient behaviours within coordination polymers functional molecular prearrangements.

Four Cd(II)/diene coordination polymers (CPs) with similar 1D chain motifs exhibit different photosalient (PS) behaviours in response to UV light. The [2+2] photoreaction between the CC groups within these CPs results in diverse PS behaviours of their crystals with different CC pair arrangements. The interesting PS behaviours of these CPs can be applied in design and fabrication of advanced photoactuating materials.

Tuning the configuration of the flexible metal-alkene-framework affords pure cycloisomers in solid state photodimerization.

The photochemical [2+2] cycloaddition of 3,5-bis-(2-(pyridin-4-yl)vinyl)pyridine (bpvp) in the flexible Cd-based metal-alkene frameworks produced different isomeric photoproducts depending on the auxiliary and guest molecules. The bulkiness of the guest molecules influenced the conformation of the ligand, and thus the outcome of the cycloaddition reaction.

[Effects of Film Materials on Ammonia Volatilization Emissions from a Paddy System After Reducing Nitrogen Fertilizer Application].

Ammonia volatilization emissions constitute the main pathway of nitrogen loss from paddy systems. Present control technologies are based on reducing the amount of nitrogen fertilizer applied. However, ratio of nitrogen loss through ammonia volatilization emissions has not changed, and it has become a bottleneck for promoting nitrogen use efficiency.

Cyclometalated Iridium(III) Complexes as High-Sensitivity Two-Photon Excited Mitochondria Dyes and Near-Infrared Photodynamic Therapy Agents.

Photodynamic therapy (PDT) using two-photon near-infrared light excitation is a very effective way to avoid the use of short-wavelength ultraviolet or visible light which cannot efficiently penetrate into the biological tissues and is harmful to the healthy cells. Herein, a series of cyclometalated Ir(III) complexes with a structurally simple diimine ligand were designed and the synthetic route and preparation procedure were optimized, so that the complexes could be obtained in apparently higher yield, productivity, and efficiency in comparison to the traditional methods. Their ground state and excited singlet and triplet state properties were studied by spectroscopy and quantum chemistry theoretical calculations to investigate the effect of substituent groups on the photophysical properties of the complexes.

Modulating the regioselectivity of solid-state photodimerization in coordination polymer crystals.

Coordination polymers [Cd(1,4-bpeb)(L1)] (1), [Zn2(1,4-bpeb)2(L2)2(SO42-)2] (2) and [Cd(1,4-bpeb)(L3)] (H2O) (3) (H2L1, 3-[2-(3-hydroxy-phenoxymethyl)-benzyloxy]-benzoic acid; HL2, 1H-Indazole-3-carboxylic acid; H3L3, benzene-1,2,3-tricarboxylic acid; 1,4-bpeb, 1,4-bis[2-(4-pyridyl)vinyl]benzene have been synthesized under solvothermal conditions. Complexes 1-3 underwent photodimerization in the solid-state to give quantitative yields of single isomeric products. The choice of carboxyl ligands L and metal center determined the arrangement of 1,4-bpeb ligands, which in turn directed the regiochemistry of the final photoproducts.

Coordination-Driven Stereospecific Control Strategy for Pure Cycloisomers in Solid-State Diene Photocycloaddition.

To obtain a pure product without the isomer byproducts is a goal that many chemists are pursuing. As one kind of very important synthesis method, the photochemical reaction is simple and straightforward yet low-selective. In this work, a coordination interaction-based oriented synthesis strategy has been proposed to realize the precise stereochemical control of the isomeric cyclic compounds in the photocycloaddition reaction.

Identification and Characterizations of Novel, Selective Histone Methyltransferase SET7 Inhibitors by Scaffold Hopping- and 2D-Molecular Fingerprint-Based Similarity Search.

SET7, serving as the only histone methyltransferase that monomethylates 'Lys-4' of histone H3, has been proved to function as a key regulator in diverse biological processes, such as cell proliferation, transcriptional network regulation in embryonic stem cell, cell cycle control, protein stability, heart morphogenesis and development. What's more, SET7 is involved inthe pathogenesis of alopecia aerate, breast cancer, tumor and cancer progression, atherosclerosis in human carotid plaques, chronic renal diseases, diabetes, obesity, ovarian cancer, prostate cancer, hepatocellular carcinoma, and pulmonary fibrosis. Therefore, there is urgent need to develop novel SET7 inhibitors.

Plantadeprate A, a Tricyclic Monoterpene Zwitterionic Guanidium, and Related Derivatives from the Seeds of Plantago depressa.

Two new alkaloids, plantadeprate A (1) and 1'-(4″-hydroxybutyl)plantagoguanidinic acid (2), along with three known compounds, were isolated from the seeds of Plantago depressa. Their structures were elucidated by physical data analyses including NMR, MS, and electronic circular dichroism (ECD) methods. Plantadeprate A (1), a monoterpene zwitterionic guanidium, possesses a unique 5/5/6-tricyclic ring system.

PTP1B inhibitors from stems of Angelica keiskei (Ashitaba).

Three new chalcones, xanthoangelols K-M (1-3), together with 19 known compounds were isolated from the stems of Angelica keiskei Koidzumi, a well-known rejuvenated and anti-diabetic plant originated from Japan. The structures of compounds 1-3 were elucidated on the basis of spectroscopic data and Mosher's method. All compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).