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Flammulina velutipes, (Curt. ex Fr.) Sing, a popularly edible fungus, has been widely used both as a restorative drug and a tonic food in China. In the current study, the effect of F. velutipes polysaccharides was evaluated with a constipated rat model induced by loperamide hydrochloride. The rats were divided into six groups: normal group, model group, positive control group, F. velutipes polysaccharides high, moderate and low dose groups. Rats were given 2 mL of Loperamide hydrochloride (3 mg·kg·d), by intragastric administration 2 times per day for 10 days. F. velutipes polysaccharides at the doses of 600, 400 and 200 mg/kg (1 mL/100g weight) were administered to treat rats with constipation for 7 days. The gastrointestinal hormones, including motilin (MTL), gastrin (GAS), substance P (SP), somatostatin (SS), and intestinal propulsive rate and feces weight at 24 hours after treatment were used as the indexes to evaluate the effects of F. velutipes polysaccharides on constipation. The levels of MTL, GAS and SP in serum significantly increased and the levels of SS in serum of rats significantly decreased after the treatment of rats with F. velutipes polysaccharides as compared with those of rats in the model group.

There are a number of secondary metabolites having medicinal values in Ligustri Lucidi Fructus. In this study, the target analytes salidroside, ligustroflavone, specnuezhenide, oleuropein, oleanolic acid and ursolic acid were chosen, aiming to establish a method to investigate the content of six compounds during eight growth stages of Ligustri Lucidi Fructus. Even though the results indicated that the contents of six compounds in different growth periods reached their maximum value, they displayed a downward trend. The antioxidant activity of the analyzed samples also decreased along with the growth period. The relationship between the content of six secondary metabolites and the activity has been elucidated. Hence, this research provides a theoretical basis for guiding efficient use of Ligustri Lucidi Fructus.

The ubiquitous bacterial second messenger c‐di‐GMP is synthesized by diguanylate cyclase and degraded by c‐di‐GMP‐specific phosphodiesterase. The genome of Pseudomonas putida contains dozens of genes encoding diguanylate cyclase/phosphodiesterase, but the phenotypical–genotypical correlation and functional mechanism of these genes are largely unknown. Herein, we characterize the function and mechanism of a P. putida phosphodiesterase named DibA. DibA consists of a PAS domain, a GGDEF domain, and an EAL domain. The EAL domain is active and confers DibA phosphodiesterase activity. The GGDEF domain is inactive, but it promotes the phosphodiesterase activity of the EAL domain via binding GTP. Regarding phenotypic regulation, DibA modulates the cell surface adhesin LapA level in a c‐di‐GMP receptor LapD‐dependent manner, thereby inhibiting biofilm formation. Moreover, DibA interacts and colocalizes with LapD in the cell membrane, and the interaction between DibA and LapD promotes the PDE activity of DibA. Besides, except for interacting with DibA and LapD itself, LapD is found to interact with 11 different potential diguanylate cyclases/phosphodiesterases in P. putida, including the conserved phosphodiesterase BifA. Overall, our findings demonstrate the functional mechanism by which DibA regulates biofilm formation and expand the understanding of the LapD‐mediated c‐di‐GMP signaling network in P. putida. [ABSTRACT FROM AUTHOR]

Diabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague–Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current–voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications. [ABSTRACT FROM AUTHOR]

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats. [ABSTRACT FROM AUTHOR]