Diarrhoea is a common clinical condition; its pathogenesis is strongly associated with gut microbiota dysbiosis. Limonitum is a well-known traditional Chinese medicine that exerts appreciable benefits regarding the amelioration of diarrhoea. However, the mechanism through which Limonitum ameliorates diarrhoea remains unclear. Here, the efficacy and underlying mechanism of Limonitum decoction (LD) regarding diarrhoea were explored from the aspect of gut microbiota. Castor oil (CO) was used to induce diarrhoea in mice, which were then used to evaluate the effects of LD regarding the timing of the first defecation, diarrhoea stool rate, degree of diarrhoea, diarrhoea score, intestinal propulsive rate, and weight of intestinal contents. The concentrations of short-chain fatty acids (SCFAs), including acetic, propionic, isobutyric, butyric and valeric acids, were analysed by gas chromatography-mass spectrometry (GC-MS). The 16S rRNA high-throughput sequencing technology was applied to evaluate changes in the gut microbiota under exposure to LD. LD was found to effectively ameliorate the symptoms of diarrhoea, and the diversity and relative abundance of gut microbiota were restored to normal levels following LD treatment. Additionally, LD significantly restored the observed reductions in SCFAs. These results provide strong evidence that LD can sufficiently ameliorate diarrhoea in mice by regulating their gut microbiota. The findings presented here highlight that Limonitum may constitute a prospective remedy for diarrhoea.

The nucleus is the most prominent organelle in eukaryotic cells, and its deformation depends on interactions between the nuclear lamina (NL) and cytoskeleton structural tensions. The structural tensions can be quantified at a pico-Newton (pN) level using a genetically encoded optical probe. In living cells, NL tensions countered the 4.26pN resting strain imposed competitively by cytoskeletal tension. The depolymerization of microfilaments or microtubules drove an aberrant increase in outward osmotic pressure through the production of mass protein-nanoparticles. The osmotic pressure also served as a directional converter of inward cytoskeletal force, and contributed to the outward expansion of NL via the passive pull of intermediate filaments (IFs). The NL, but not IFs, can remotely detect extracellular osmosis pressure alterations, which are closely associated with highly polarized microfilament and microtubule structures and their directional force activities. The oxidative-induced increase of NL tension results from intracellular hyper-osmosis, associated closely with protein-nanoparticles production elicited by cofilin and stathmin activation. These data reveal that intracellular steerable forces interact direction-dependently to control NL tension in terms of their magnitude and vectors. 15 . IF tension exerts pulling forces on the nucleus, which serves as a "piston" with the function of osmotic pressure. Furthermore, osmotic pressure-induced IF tension can be reversed by MF and MT tensions in the phenomenon of regulatory volume decrease (RVD) 14 .MFs and MTs, unlike IFs, are highly polarized 16 . The organization of the MF and MT network in cells, where plus ends are found adjacent to the membrane and minus ends are located toward the cytoplasm, imply their role in pulling or pushing plasma membrane and nuclear envelope [17][18][19] . Myosin has a role in prograde transport along MFs toward the membrane. Most kinesin proteins move towards the microtubule plus ends 15, 20 , whereas cytoplasmic dynein locates along the minus-end-directed motor in the cell 21,22 . The direction of cytoskeletal structural tensions is dependent upon the organization of the cytoskeletal meshwork and the direction of the molecular motor 16,23 . Meanwhile, tension due to MFs and MTs could be eliminated if MFs and MTs are depolymerized into actin and tubulin monomers or macromolecular polymers of size 1-100 nm [24][25][26] . Generation of these nanoparticle was thought to result in the colloid OP. However, the mechanisms that underpin the interactions between external forces and internal stresses in nucleoskeletal alterations remains poorly understood.Nuclear deformation can be induced in live cells in response to chemical trigger signals, which may be associated with senescence 7 , oxidative stress 27, 28 , and apoptosis-related changes 29, 30 . These activities have all been identified as mechanosensitive elements that can activate cytoskeletal structural tension 31,32 . Tension can be rapidly redistributed at a subcellular level a...