Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids and nucleotides and an important carbon source in the tricarboxylic acid (TCA) cycle and lipid biosynthesis pathway. In this review, we summarize the significant role of glutamine metabolism in tumor development and highlight the vulnerabilities of targeting glutamine metabolism for effective therapy. In particular, we review the reported drugs targeting glutaminase and glutamine uptake for efficient cancer treatment. Moreover, we discuss the current clinical test about targeting glutamine metabolism and the prospective direction of drug development.

Exploiting the Achilles’ heel of cancer: disrupting glutamine metabolism for effective cancer treatment

Major health events caused by pathogenic microorganisms are increasing, seriously jeopardizing human lives. Currently PCR and ITA are widely used for rapid testing in food, medicine, industry and agriculture. However, due to the non-specificity of the amplification process, researchers have proposed the combination of nucleic acid amplification technology with the novel technology CRISPR for detection, which improves the specificity and credibility of results. This paper summarizes the research progress of nucleic acid amplification technology in conjunction with CRISPR/Cas technology for the detection of pathogens, which provides a reference and theoretical basis for the subsequent application of nucleic acid amplification technology in the field of pathogen detection.

Combination of nucleic acid amplification and CRISPR/Cas technology in pathogen detection

Recently, researchers have expanded the investigation into attentional biases toward positive stimuli; however, few studies have examined attentional biases toward positive auditory information. In three experiments, the present study employed an emotional spatial cueing task using emotional sounds as cues and auditory stimuli (Experiment 1) or visual stimuli (Experiment 2 and Experiment 3) as targets to explore whether auditory or visual spatial attention could be modulated by positive auditory cues. Experiment 3 also examined the temporal dynamics of cross-modal auditory bias toward positive natural sounds using event-related potentials (ERPs). The behavioral results of the three experiments consistently demonstrated that response times to targets were faster after positive auditory cues than they were after neutral auditory cues in the valid condition, indicating that healthy participants showed a selective auditory attentional bias (Experiment 1) and cross-modal attentional bias (Experiment 2 and Experiment 3) toward positive natural sounds. The results of Experiment 3 showed that N1 amplitudes were more negative after positive sounds than they were after neutral sounds, which further provided electrophysiological evidence that positive auditory information enhances attention at early stages in healthy adults. The results of the experiments performed in the present study suggest that humans exhibit an attentional bias toward positive natural sounds.

https://www.frontiersin.org/articles/10.3389/fnhum.2022.949655/pdf

Auditory and cross-modal attentional bias toward positive natural sounds: Behavioral and ERP evidence

Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit the development of synthetic chemistry, pharmaceutical research, and materials science. Substituted amines, especially nitrogen-containing alkyl heterocyclic compounds, are widely found in nature products and drugs. Generally, accessing these compounds requires multiple steps, which could result in low efficiency. In this work, a molecular editing strategy is used to realize the synthesis of nitrogen-containing compounds using aryl alkanes as starting materials. Using derivatives of O-tosylhydroxylamine as the nitrogen source, this method enables precise nitrogen insertion into the Csp 

Selective nitrogen insertion into aryl alkanes

BACKGROUND
Lysophosphatidic acids (LPAs) belong to a class of bioactive lysophospholipids with multiple functions including immunomodulatory roles in tumor microenvironment (TME). LPA exerts its biological effects via its receptors that are highly expressed in fibroblasts among other cell types. As cancer-associated fibroblasts (CAFs) are a key component of the TME, it is important to understand LPA signaling and regulation of receptors in fibroblasts or CAFs and associated regulatory roles on immunomodulation-related molecules.


METHODS
Cluster analysis, immunoblotting, real-time quantitative-PCR, CRISPR-Cas9 gene editing system, immunohistochemical staining, coculture model, and in vivo xenograft model were used to investigate the effects of LPA-LPAR1 on B7-H3 in tumor promotion of CAFs.


RESULTS
In this study, we found that LPAR1 and CD276 (B7-H3) were generally highly expressed in fibroblasts with good expression correlation. LPA induced B7-H3 up-expression through LPAR1, and stimulated fibroblasts proliferation that could be inhibited by silencing LPAR1 or B7-H3 as well as small molecule LPAR1 antagonist (Ki16425). Using engineered fibroblasts and non-small cell lung carcinoma (NSCLC) cell lines, subsequent investigations demonstrated that CAFs promoted the proliferation of NSCLC in vitro and in vivo, and such effect could be inhibited by knocking out LPAR1 or B7-H3.


CONCLUSION
The present study provided new insights for roles of LPA in CAFs, which could lead to the development of innovative therapies targeting CAFs in the TME. It is also reasonable to postulate a combinatory approach to treat malignant fibrous tumors (such as NSCLC) with LPAR1 antagonists and B7-H3 targeting therapies.

Disruption of LPA-LPAR1 pathway results in lung tumor growth inhibition by downregulating B7-H3 expression in fibroblasts.

In attentional orienting, researchers have proposed that reward history is a component of attentional control, as the reward value might enhance the spatial attention process to achieve more efficient goal-directed behavior and to improve target-detection performance. Although the effect of reward–induced motivation on attentional orienting has been studied in two–dimensional (2-D) space, the specific mechanisms underlying the influence of reward on inhibition of return (IOR) of attentional orienting in three-dimensional space (3-D) remain unclear. In the present study, by incorporating the Posner spatial-cueing paradigm into a virtual 3-D environment, we aimed to investigate the influence of reward on IOR in 3-D space. The results showed the following: (1) IOR size in the rewarded conditions was smaller than IOR size in the unrewarded condition in the near depth plane, resulting in an IOR difference with or without reward. (2) Reward weakened IOR in the near depth plane because the response to the uncued location was delayed, not because the response to the cued location was accelerated. The present study indicated that the different depth planes of the target location in 3-D space could influence the interaction between reward and IOR, and reward weakened IOR in the near depth plane.

Reward Weakened Inhibition of Return (IOR) in the Near Depth Plane

Hormetic effects of EGC and EGCG on CES1 activity and its rescue from oxidative stress in rat liver S9.

Antitumor activity of mianserin (a tetracyclic antidepressant) primarily driven by the inhibition of SLC1A5-mediated glutamine transport

Reacting to a moving object requires an ability to estimate when a moving object reaches its destination, also referred to as the time-to-contact (TTC) estimation. Although the TTC estimation of threatening visually moving objects is known to be underestimated, the effect of the affective content of auditory information on visual TTC estimation remains unclear. We manipulated the velocity and presentation time to investigate the TTC of a threat or non-threat target with the addition of auditory information. In the task, a visual or an audiovisual target moved from right to left and disappeared behind an occluder. Participants’ task was to estimate the TTC of the target, they needed to press a button when they thought that the target contacted a destination behind the occluder. Behaviorally, the additional auditory affective content facilitated TTC estimation; velocity was a more critical factor than presentation time in determining the audiovisual threat facilitation effect. Overall, the results indicate that exposure to auditory affective content can influence TTC estimation and that the effect of velocity on TTC estimation will provide more information than presentation time.

/pdf/auditory-affective-content-facilitates-time-to-contact-2ciu519k.pdf

Auditory affective content facilitates time-to-contact estimation of visual affective targets

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