Xinyao Wang

Background and Purpose: New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of basolateral amygdala (BLA) astrocytes in DNP pathogenesis and provide new insights into therapeutic strategies for DNP.Experimental Approach: A streptozotocin‐induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate astrocyte activity. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety‐like behaviours were detected using open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA.Key Results: BLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and pain‐related negative emotions in DNP rats. In contrast, temporary activation of BLA astrocytes induced allodynia without anxious behaviours in naive rats. In addition, koumine (KM) alleviated mechanical allodynia and anxiety‐like behaviours in DNP rats, inhibited the activation of BLA astrocytes and suppressed the inflammatory response. Furthermore, persistent activation of BLA astrocytes through chemogenetics mimicked chronic pain, and KM alleviated the pain hypersensitivity and anxiety‐like behaviours.Conclusion and Implications: DREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocyte activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. KM ameliorates DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.

The Jurassic continental shale oil (gas) is a favorable unconventional resource in the Sichuan Basin of China. In this paper, analysis methods such as core and outcrops observation, thin section identification, scanning electron microscopy (SEM), and X-ray diffraction (XRD) are used to describe the characteristics of lacustrine fine-grained rock reservoir in Da’anzhai Member of the Ziliujing Formation in Sichuan Basin, and it discussed the influence and control of lacustrine fine-grained rock diagenesis on the quality of the reservoir, in order to determine the shale reservoir control factors. The results show that there are three types of rocks in the Da’anzhai Member, which are mudstone, siltstone, and limestone, and the rock combination of shell shale intercalated with shell limestone is developed in the Da 2 submember. Fine-grained sedimentary rocks in this section have undergone compaction, cementation, dissolution, metasomatism, transformation of clay minerals, and hydrocarbon generation of organic matter, which are currently in the middle diagenetic stage A or B substage. Compaction and cementation are the main factors that control the physical use of shale and limestone, and strong cementation is the main reason for the tightness of limestone reservoirs in the Da’anzhai Member in the northern and eastern parts of Sichuan Basin. The difference between dissolution and cementation is the main control factor for the formation of limestone or argillaceous limestone reservoirs in the same section in central Sichuan Basin. The organic-rich shale and shell shale of the Yuanba and Fuling area are the most favorable reservoirs of the Ziliujing Formation in this region. The shell limestone that experienced favorable dissolution in the Da’anzhai Member in the central of the Sichuan Basin has become a limestone reservoir. Discussing the impact of continental fine-grained rock diagenesis on the reservoir can better explore and develop similar intervals, enrich unconventional shale oil and gas accumulation and storage theories, and provide basic theoretical support for finding favorable unconventional shale oil and gas reservoirs.