Discovery of Benzo[]oxazoles as Novel Dual Small-Molecule Inhibitors Targeting PD-1/PD-L1 and VISTA Pathway.

The blockers of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway have achieved great clinical success. However, the limited efficacy and low tumor response rate of anti-PD-1/PD-L1 monotherapy limit the clinical application of PD-1/PD-L1 inhibitors. V-domain immunoglobulin suppressor of T-cell activation (VISTA), a novel checkpoint regulator, exhibits potential synergy with PD-1/PD-L1 in enhancing antitumor immunity.

Discovery of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives as tubulin polymerization inhibitors for anticancer therapy: The in vitro and in vivo biological evaluation.

A series of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives were designed, synthesized and estimated for their in vitro antiproliferative activities against HepG2, U251, PANC-1, A549 and A375 cell lines. Among them, compound 32 was the most promising candidate, and displayed strong broad-spectrum anticancer activity. The mechanism studies revealed that compound 32 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, and induced apoptosis by up-regulating the expression of cleaved PARP-1 and caspase-3.

Evaluation of adverse reactions induced by anti-tuberculosis drugs among hospitalized patients in Wuhan, China: A retrospective study.

The study aims to estimate the incidence and risk factors of adverse drug reactions (ADRs) induced by anti-tuberculosis (TB) drugs. A single center retrospective analysis of patients taking anti-TB therapy from January 2016 to December 2018 in the hospital was conducted. Univariate and multivariate logistic regression analysis were used to identify these risk factors of ADRs induced by anti-TB drugs.

An anthraquinone-based bismuth-iron metal-organic framework as an efficient photoanode in photoelectrochemical cells.

Metal-organic frameworks (MOFs) are appealing candidate materials to design new photoelectrodes for use in solar energy conversion because of their modular nature and chemical versatility. However, to date there are few examples of MOFs that can be directly used as photoelectrodes, for which they must be able to afford charge separation upon light absorption, and promote the catalytic dissociation of water molecules, while maintaining structural integrity. Here, we have explored the use of the organic linker anthraquinone-2, 6-disulfonate (2, 6-AQDS) for the preparation of MOFs to be used as photoanodes.

An off-on fluorescent nanoprobe for L-cysteine sensing based on the FRET effect.

A self-assembled fluorescent nanosensor for the determination of L-cysteine (Cys) was constructed based on the mechanism of fluorescence resonance energy transfer (FRET). In this system, CdTe/ZnS QDs serve as the energy donor while AuNPs serve as the receptor, resulting in the occurrence of FRET with dramatic fluorescence quenching of the QDs (turn off). Once Cys is added, AuNPs can adsorb Cys, leading to the release of the QDs.

Novel Benzimidazoles as Potent Small-Molecule Inhibitors and Degraders of V-Domain Ig Suppressor of T-Cell Activation (VISTA).

The V-domain Ig suppressor of T-cell activation (VISTA) is a promising negative immune checkpoint and plays a critical role in the regulation of the quiescence of naïve T lymphocytes. Most patients however do not experience durable disease control from current immune checkpoint inhibitors and discovery of inhibitors targeting novel immune checkpoints is necessary. Herein, we report our discovery and optimization of benzimidazoles as the bifunctional inhibitors of VISTA.

Constructing 3D hierarchical TiO microspheres with enhanced mass diffusion for efficient glucose photoreforming under modulated reaction conditions.

Three-dimensional (3D) TiO hierarchical microspheres (THMs) were successfully prepared via a facial template-free hydrothermal approach. The possible growth mechanism of THM was also investigated by TiCl concentration-, time-, and temperature-dependent experiments. The results indicate that the formation of an urchin-like hierarchical structure may follow a "nucleation-dissolution and recrystallization-assembly" process.

Rapid fabrication of tough sodium alginate/MXene/poly(vinyl alcohol) dual-network hydrogel electrolytes for flexible all-solid-state supercapacitors.

With the rapid development of flexible portable devices, polymer-based hydrogel electrolytes have drawn tremendous attention and widespread interest to replace conventional liquid electrolytes. Herein, an eco-friendly, low cost and fast method was adopted to synthesize novel cross-linked dual-network hydrogel electrolytes (PVA/SA/MXene-NaCl) within 5 min due to the formation of borate bonds. The unique dual-network structure of hydrogel enabled hydrogel electrolytes to efficiently dissipate energy under deformation and the formation of borate bonds endowed hydrogel with self-healing ability.

Design, synthesis, and evaluation of PD-1/PD-L1 small-molecule inhibitors bearing a rigid indane scaffold.

Discovery of small-molecule inhibitors against programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis provides a promising alternative to overcome the inevitable defects of PD-1/PD-L1 monoclonal antibodies (mAbs). Here, we report a series of indanes as novel small-molecule inhibitors of PD-1/PD-L1 interaction. Thirty-one indanes were synthesized and the structure-activity relationships (SARs) demonstrated that conformational restriction with (S)-indane is superior in potency to inhibit the interaction of PD-1 and PD-L1.

Construction of CdTe@γ-CD@RBD nanoprobe for Fe-sensing based on FRET mechanism in human serum.

A Fe optical sensor (CdTe@γ-CD@RBD) has been developed by using gamma-cyclodextrin (γ-CD) as a bridge to link CdTe quantum dots (QDs) and a Rhodamine B derivative (RBD). The RBD molecule can enter the cavity of the γ-CD anchored onto the surfaces of the QDs. In the presence of Fe, the fluorescence resonance energy transfer (FRET) process from QDs to RBD will be initiated, rendering the nanoprobe to display a response to Fe.

Drug-induced liver injury in COVID-19 patients during hospitalization.

Since coronavirus disease 2019 (COVID-19) outbreaks in December 2019 in Wuhan, almost no studies have systematically described drug-induced liver injury (DILI) in COVID-19 patients. This study aimed to assess the characteristics of liver test abnormality or liver injury in patients with COVID-19, and further to explore DILI in COVID-19 patients during hospitalization. It was a single-center retrospective analysis of confirmed severe acute respiratory syndrome coronavirus 2 infected patients in the hospital from January 2020 to March 2020.

Incidence and non-genetic risk factors of irinotecan-induced severe neutropenia in Chinese adult inpatients.

To analyze the incidence and nongenetic risk factors of irinotecan-induced severe neutropenia in the hospital, and provide additional reference and help for clinical treatment. A retrospective analysis of patients who received irinotecan based chemotherapy from May 2014 to May 2019 in Renmin Hospital of Wuhan University was conducted. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with severe neutropenia induced by irinotecan.

Sodium alginate-based gel electrodes without binder for high-performance supercapacitors.

Binder use results in an expansion of the dead volume of the active material and a decline in the active sites, which will lead to a decrease in the electrochemical activity of the electrode. Therefore, the construction of electrode materials without the binder has been the research focus. Here, a novel ternary composite gel electrode without the binder (reduced graphene oxide/sodium alginate/copper cobalt sulfide, rGSC) were designed using a convenient hydrothermal method.

Confining isolated photosensitizers to relieve self-aggregation and potentiate photodynamic efficacy for synergistic cancer therapy.

By quenching the electronic excited state, self-aggregation of photosensitizers deteriorates the photodynamic therapy (PDT) outcome. Previously reported strategies to mitigate aggregation-caused-quenching (ACQ) involve harsh conditions and tedious synthesis processes. Moreover, failure to tune the extent of photosensitizer aggregation on-demand usually leads to a sub-optimal PDT effect.

Discovery of Small-Molecule Inhibitors of the PD-1/PD-L1 Axis That Promote PD-L1 Internalization and Degradation.

Several monoclonal antibodies targeting the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway have been used successfully in anticancer immunotherapy. Inherent limitations of antibody-based therapies remain, however, and alternative small-molecule inhibitors that can block the PD-1/PD-L1 axis are urgent needed. Herein, we report the discovery of compound as a bifunctional inhibitor of PD-1/PD-L1 interactions.

Effective enhancement of electron migration and photocatalytic performance of nitrogen-rich carbon nitride by constructing fungal carbon dot/molybdenum disulfide cocatalytic system.

To find a cocatalyst that can replace noble metals, fungal carbon dot (CD) modified molybdenum disulfide (MoS) cocatalyst system was designed. The composites were prepared by hydrothermal and calcination methods with different ratios of CDs, MoS and nitrogen-rich carbon nitride (p-CN). p-CN has excellent electronic properties, and MoS modified by CDs (D-MoS) can significantly enhance the photocatalytic performance of p-CN by improving the photogenerated electron migration efficiency.

Design, synthesis and biological evaluation of macrocyclic derivatives as TRK inhibitors.

Tropomyosin receptor kinases (TRKA, TRKB, TRKC) are transmembrane receptor tyrosine kinases, which are respectively encoded by NTRK1, NTRK2, and NTRK3 genes. Herein, we reported the design, synthesis and Structure-Activity Relationship (SAR) investigation of a series of macrocyclic derivatives as new TRK inhibitors. Among these compounds, compound 9e exhibited strong kinase inhibitory activity (TRK IC = 13.

Novel Biphenyl Pyridines as Potent Small-Molecule Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction.

With the successful clinical application of anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) monoclonal antibodies (mAb), targeting the PD-1/PD-L1 interaction has become a promising method for the discovery of cancer therapy. Due to the inherent limitations of antibodies, it is necessary to search for small-molecule inhibitors against the PD-1/PD-L1 axis. We report the design, synthesis, and evaluation and of a series of novel biphenyl pyridines as the inhibitors of PD-1/PD-L1.

Design, synthesis and biological activity of bicyclic carboxamide derivatives as TRK inhibitors.

'precision medicine' is characterized by the selection of targeted drugs based on genetic characteristics of tumor from patients, and no longer selected basis on the type of cancer tissue. Among them, clinical trials on neurotrophin receptor tyrosine kinase genes (NTRK) have proven that great anti-cancer effects can be achieved in different cancer patients. In this paper, a novel total of twenty compounds in two categories have been designed and synthesized.

Constructing CeO/nitrogen-doped carbon quantum dot/g-CN heterojunction photocatalysts for highly efficient visible light photocatalysis.

Ternary CeO/nitrogen-doped carbon quantum dot (NCQD)/graphitic carbon nitride (g-CN) heterojunction nanocomposites were prepared by a high-temperature calcination and hydrothermal method and tested for degrading tetracycline (TC) and generating H. Compared with CeO and g-CN, the Z-scheme CeO/NCQDs/g-CN (CSNx, where x represents the amount of CeO in wt%) nanoparticles showed a higher TC photodegradation capacity and H evolution ability owing to enhanced efficient charge separation and photocatalytic stability. CSN5 showed the best photodegradation activity for TC degradation (100 mL, 20 mg L; 100% degradation in 60 min; λ≥ 420 nm) and the highest H evolution rate of 1275.

Binder-free CuS/ZnS/sodium alginate/rGO nanocomposite hydrogel electrodes for enhanced performance supercapacitors.

CuS/ZnS/sodium alginate/reduced graphene oxide nanocomposites (CZSrG) were prepared by physical crosslinking followed by one-step reduction and were justified as green binder-free hydrogel high-capacitance electrodes. The physical crosslinking was realized simply through the hydrogen-bond interaction between sodium alginate (SA) and graphene oxide (GO), avoiding the usage of traditional Ca crosslinking agent. The hydrogel structure made of CZSrG possessed the most beneficial effect of avoiding large volume change and increasing cycle stability for supercapacitors.