Erratum: Author correction to "Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning" [Acta Pharm Sin B 12 (2022) 2429-2442].

[This corrects the article DOI: 10.1016/j.apsb.

Deuteration-Driven Photopharmacology: Deuterium-Labeled for Controlling Alpha 7 Nicotinic Acetylcholine Receptors.

Photopharmacology is a powerful approach to investigate biological processes and overcomes the common therapeutic challenges in drug development. Enhancing the photopharmacology properties of photoswitches contributes to extend their applications. Deuteration, a tiny structural modification, makes it possible to improve the photopharmacology and photophysical properties of prototype compounds, avoiding extra complex chemical changes or constructing multicomponent systems.

Progress in Rice Breeding Based on Genomic Research.

The role of rice genomics in breeding progress is becoming increasingly important. Deeper research into the rice genome will contribute to the identification and utilization of outstanding functional genes, enriching the diversity and genetic basis of breeding materials and meeting the diverse demands for various improvements. Here, we review the significant contributions of rice genomics research to breeding progress over the last 25 years, discussing the profound impact of genomics on rice genome sequencing, functional gene exploration, and novel breeding methods, and we provide valuable insights for future research and breeding practices.

Machine learning-based identification of CYBB and FCAR as potential neutrophil extracellular trap-related treatment targets in sepsis.

Objective: Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown.

Near-Infrared Ratiometric Hemicyanine-Based pH Fluorescence Probe with Bone Targetability for Monitoring Bone Resorption.

Accurate detection of bone resorption is extremely important in the orthodontic treatment process as it can provide a basis for clinical treatment strategies. Recently, pH-responsive fluorescence probes have received tremendous attention in bone resorption monitoring owing to their high sensitivity, good specificity, and in situ and real-time detection capabilities, but there are still some shortcomings like the increase in the risk of osteonecrosis of the jaw by use of bisphosphonate as the bone-targeting moiety and the insufficient monitoring accuracy due to susceptibility to interference. Herein, we designed and synthesized a near-infrared ratiometric hemicyanine-based pH fluorescence probe (Hcy-Asp6) with fluorescence-imaging and pH-determining capabilities, and bone targetability for more reliably and safely monitoring the bone resorption in orthodontic treatment.

Identification of anthelmintic parbendazole as a therapeutic molecule for HNSCC through connectivity map-based drug repositioning.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common human cancers; however, its outcome of pharmacotherapy is always very limited. Herein, we performed a batch query in the connectivity map (cMap) based on bioinformatics, queried out 35 compounds with therapeutic potential, and screened out parbendazole as a most promising compound, which had an excellent inhibitory effect on the proliferation of HNSCC cell lines. In addition, tubulin was identified as a primary target of parbendazole, and the direct binding between them was further verified.

Photophosphatidylserine Guides Natural Killer Cell Photoimmunotherapy Tim-3.

Natural killer (NK) cells, in addition to their cytotoxicity function, harbor prominent cytokine production capabilities and contribute to regulating autoimmune responses. T-cell immunoglobulin and mucin domain containing protein-3 (Tim-3) is one of the inhibitory receptors on NK cells and a promising immune checkpoint target. We recently found that phosphatidylserine (PS) binding to Tim-3 can suppress NK cell activation.

Constructing firefly luciferin bioluminescence probes for imaging.

Bioluminescence imaging (BLI) is a widely applied visual approach for real-time detecting many physiological and pathological processes in a variety of biological systems. Based on the caging strategy, lots of bioluminescent probes have been well developed. While the targets react with recognizable groups, caged luciferins liberate luciferase substrates, which react with luciferase generating a bioluminescent response.

Discovery of small-molecule fluorescent probes for C-Met.

C-mesenchymal-epithelia transition factor (c-Met) is highly expressed in various solid tumors such as gastric cancer, liver cancer, and lung cancer, playing a pivotal role in the growth, maintenance, and development of different tumor cells. In this study, three small-molecule fluorescent probes (5, 11, 16) targeting c-Met were developed, and their design strategies were also initially explored. In general, the fluorescence properties of the probes themselves could meet the imaging requirements, and they have shown sufficient inhibitory activities against c-Met, especially probe 16, reflecting the targeting and acceptance.

Polarity-based fluorescence probes: properties and applications.

Local polarity can affect the physical or chemical behaviors of surrounding molecules, especially in organisms. Cell polarity is the ultimate feedback of cellular status and regulation mechanisms. Hence, the abnormal alteration of polarity in organisms is closely linked with functional disorders and many diseases.

Bacteria-Based Live Vehicle for Bioluminescence Imaging.

The anticancer therapy strategy mediated by tumor-targeting bacteria needs better visualization tools for imaging and monitoring bacteria . The probiotic strain Nissle 1917 (EcN), one of the tumor-targeting bacteria, leads to the potential application for cancer therapy. Here, we report the development and application of a live, EcN-based imageable vehicle for noninvasive bioluminescence imaging in live mice.

Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC).

The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this issue, in which they can be triggered by ultraviolet A (UVA) or visible light to induce the degradation of the target protein.

Photoinduced Electron Transfer-Based Fluorescent Agonists for α-Adrenergic Receptors Imaging.

The novel fluorescent agonists were discovered herein for α-adrenergic receptors (α-ARs) based on photoinduced electron transfer (PeT) off-on switch by conjugating the fluorophore 7-(diethylamino)coumarin-3-carboxylic acid with phenylephrine. After careful evaluation, these probes exhibited efficient binding affinity with α-ARs and could be applied to selectively imaging α-ARs or successfully tracing the dynamic process of α-AR internalization in living cells. Meanwhile, a bioluminescence resonance energy transfer binding assay with these new probes has been well-established and applied.

Optical Control of CRAC Channels Using Photoswitchable Azopyrazoles.

The Ca release-activated Ca (CRAC) channels control many Ca-modulated physiological processes in mammals. Hyperactivating CRAC channels are known to cause several human diseases, including Stormorken syndrome. Here, we show the design of azopyrazole-derived photoswitchable CRAC channel inhibitors (designated ), which enable optical inhibition of store-operated Ca influx and downstream signaling.

Discovery of Environment-Sensitive Fluorescent Agonists for α-Adrenergic Receptors.

A series of novel fluorescent agonists were well developed herein with turn-on switch for α-adrenergic receptors (α-ARs) by conjugating the environment-sensitive fluorophore 4-chloro-7-nitrobenzoxadiazole with phenylephrine. Overall, these probes exhibited efficient binding and apparent fluorescence intensity changes (up to 10-fold) upon binding with α-ARs. Moreover, these probes have been successfully applied for selectively imaging α-ARs in the living cells.

Novel photoactivatable substrates for Renilla luciferase imaging in vitro and in vivo.

To develop a photoactivatable bioluminescence imaging technique, a set of high and efficient photoactivatable substrates for Renilla luciferase has been well designed and synthesized. Surprisingly, all of them could release the free luciferin that presented robust bioluminescent signals ex vivo and in living animals after UV irradiation at 365 nm.

Pharmacokinetics and tolerability of cinitapride in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study.

Cinitapride (CIN) is a drug for functional dyspepsia. The purpose of the study was to investigate the pharmacokinetics and tolerability of CIN in healthy Chinese volunteers. A randomized, open-label, single- and multiple-dose study was conducted in 12 healthy volunteers.

A coelenterazine-type bioluminescent probe for nitroreductase imaging.

Novel coelenterazine-type bioluminescent probes have been designed and synthesized to detect nitroreductase (NTR) in hypoxic tumors. The design strategy is that NTR catalyzes the reduction of the nitrobenzyl moiety to the aniline group with an electron donor, thus resulting in 1,4 or 1,6-rearrangement-elimination to release coelenterazine analogues, which can be catalyzed by Renilla luciferase to emit bioluminescence. After careful evaluation, almost all probes had a 3-fold greater response for NTR over other biologically relevant substances at >100-fold dose more than NTR.

Prolonged bioluminescence imaging in living cells and mice using novel pro-substrates for Renilla luciferase.

The prodrug or caged-luciferin strategy affords an excellent platform for persistent bioluminescence imaging. In the current work, we designed and synthesized ten novel pro-substrates for Renilla luciferase by introducing ester protecting groups of different sizes into the carbonyl group of the free luciferin 1. Taking advantage of intracellular esterases, lipases, and nucleophilic substances, the ester protecting groups were hydrolyzed, resulting in the release of a free luciferin and a bioluminescence signal turn-on.

New bioluminescent coelenterazine derivatives with various C-6 substitutions.

A series of new coelenterazine analogs with varying substituents at the C-6 position of the imidazopyrazinone core have been designed and synthesized for the extension of bioluminescence substrates. Some of them display excellent bioluminescence properties compared to DeepBlueC™ or native coelenterazine with both in vitro and in vivo biological evaluations, thus placing these derivatives among the most ideal substrates for Renilla bioluminescence applications.

A novel coelenterate luciferin-based luminescent probe for selective and sensitive detection of thiophenols.

The first dual bioluminescent and chemiluminescent sensor for detecting highly toxic thiophenols has been developed. Such a probe was designed by using a coelenterazine analogue as the luminophore and dinitrophenyl ether as the recognition moiety. It should be noted that this probe displayed good sensitivity and selectivity toward thiophenols, and has been effectively applied for the quantitative detection of thiophenols in aqueous media and complex biological samples.

Pharmacokinetics and Bioequivalence Study of Hydroxychloroquine Sulfate Tablets in Chinese Healthy Volunteers by LC-MS/MS.

Introduction: Hydroxychloroquine (HCQ), 4-aminoquinoline, is an antimalarial drug and has become a basic therapy for rheumatic disease treatment. It can stabilize the condition of SLE patients and reduce the chances of patient relapse through its immunosuppressive function and antiinflammatory effects. This drug was absorbed completely and rapidly by oral administration, but has a prolonged half-life for elimination.

Novel bioluminescent coelenterazine derivatives with imidazopyrazinone C-6 extended substitution for Renilla luciferase.

Two series of novel coelenterazine analogues (alkynes and triazoles) with imidazopyrazinone C-6 extended substitution have been designed and synthesized successfully for the extension of bioluminescent substrates. After extensive evaluation, some compounds display excellent bioluminescence properties compared with DeepBlueC in cellulo, thus becoming potential molecules for bioluminescence techniques.

A Randomized, Clinical Trial Involving Different Surgical Methods Affecting the Sphincter of Oddi in Patients With Choledocholithiasis.

Aim: The purpose of the current study was to compare pressure changes in the sphincter of Oddi (SO) and stone recurrence after surgery in patients with choledocholithiasis who underwent laparoscopic common bile duct exploration during laparoscopic cholecystectomy (LC) or endoscopic sphincterotomy (EST) with LC, which may provide clinical evidence for choledocholithiasis patients to choose the appropriate surgical approach.

Materials And Methods: Fifty-one patients with choledocholithiasis were randomized to the EST/LC (group A 26 cases) or laparoscopic common bile duct exploration during LC group (group B 25 cases). We performed SO manometry during surgery and 3 months postoperatively on all patients.