Diarrhea-predominant irritable bowel syndrome (IBS-D) is one common chronic functional disease of the digestive system with limited treatments. The microbiota–gut–brain axis (MGBA) has a central function in the pathogeny of IBS-D, which includes the participation of many various factors, such as brain-gut peptides (BGPs), immune inflammation, and intestinal flora. Inspired by the drug combination in traditional Chinese medicine (TCM), our previous study discovered that berberine (BBR) and baicalin (BA) could form natural self-assemblies as BA-BBR nanoparticles (BA-BBR NPs) and showed synergistic effects against IBS-D. Here, we investigated the synergistic effects of BA-BBR NPs on IBS-D model mice induced by chronic restraint stress plus Senna alexandrina Mill decoction with the influence on MGBA. BA-BBR NPs showed the best therapeutic effect on improving visceral hypersensitivity and diarrhea on IBS-D model mice, compared with BBR, BA, and BA/BBR mixture. Furthermore, BA-BBR NPs significantly ( P <0.05) reduced the levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal polypeptide (VIP) and choline acety transferase (CHAT) in colon tissues or of serum from BGPs; it lowered the expressions of the nuclear factor kappa-B (NF-κB) in colon tissues and changed the levels of basophil granulocyte (BASO) and leukomonocyte (LYMPH) in whole blood from immune inflammation; it altered the intestinal flora of Bacteroidia, Deferribacteres, Verrucomicrobia, Candidatus_Saccharibacteria, and Cyanobacteria from intestinal flora. In conclusion, BA-BBR NPs, after forming the natural self-assembly between BBR and BA, promoted the synergistic effect on IBS-D mice than the sum of BBR and BA effects, based to the formation of self-assemblies rather than the simple mixing. It further proved that synergistic effect of BA-BBR NPs on IBS-D mice might be related to BGPs, immune inflammation, and intestinal flora from three important interrelated components of MGBA. This study will provide a novel idea for the interpretation of TCM compatibility theory and provide the basis for BA-BBR NPs as a medicinal plant-derived natural and efficient nanomaterial for clinical use.

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Market research shows that the global 3D printing market size was $16.54 billion in 2021 and is expected to have a growth rate of 21.0% from 2021 to 2028. The global market will reach around $63 billion by 2028. [1] 3D printing has been used in different environments ranging from ambient home and office use, bioimplant printing, to zero gravity space 3D printing, such as functional living organism's body parts, [2] and zero-gravity 3D printing in the international space station. [3] Apart from lab printing of delicate designs, 3D printing technology is being used for industrial [4] and construction [5] purposes. It has gained research and industrial interests in broad areas, including biomedical applications, [6,7] lightweight engineering materials, [7][8][9][10] electronics and sensors, [11] fiber-reinforced and multifunctional composites, [8,9,[12][13][14][15][16][17] and shape morphing designs. [6,18] Among different 3D printed devices, 3D printed sensors have been attracting significant attention. In sensors manufacturing, it is important for 3D printing of complementary accessories, embedded sensing components, as well as seamless fabrication of whole sensors [19] .Traditional manufacturing methods, such as coating and injection molding, are incompatible for fabricating complex structured sensors.

Background Jinshuibao capsules (JSB) have been widely used to treat early diabetic nephropathy (DN), but the specific effects are still inconsistent. A meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the clinical efficacy of JSB for early DN. Methods Four international databases and four Chinese databases were searched from publication dates to March 1, 2018. The RCTs reporting the results of JSB's specific effects were included, and comparisons were between JSB combined with Angiotensin Receptor Blockers (ARBs) as experimental intervention and ARBs as the control. Included studies' quality was evaluated and the extracted data were analyzed with RevMan 5.3 software. Results Twenty-six RCTs including 2198 early DN participants were adopted in the meta-analysis. The results showed that, compared with the ARBs alone, JSB could remarkably improve the ORR (OR = 3.84; 95% CI: 2.37~6.24; P < 0.00001) and decrease 24 h UTP (MD = −93.32; 95% CI: −128.60 ~−58.04; P < 0.00001), UAER (MD = −24.02; 95% CI: −30.93 ~−17.11; P < 0.00001), BUN (MD = −0.26; 95%: −0.44 ~−0.08; P = 0.005), Scr (MD = −9.07; 95% CI: −14.26 ~−3.88; P = 0.0006), ACR (MD = −17.55; 95% CI: −22.81 ~−12.29; P < 0.00001), Cys-C (MD = −0.60; 95% CI: −0.88 ~−0.32; P < 0.00001), SBP (MD = −3.08; 95% CI: −4.65 ~−1.52; P = 0.0001), DBP (MD = −2.09; 95% CI: −4.00 ~−0.19; P = 0.03), and TG (MD = −0.36; 95% CI: −0.50 ~−0.21; P < 0.00001). However, it showed no significant differences in TC (MD = −0.32; 95% CI: −0.69~0.04; P = 0.08), FBG (MD = 0.04; 95% CI: −0.39~0.47; P = 0.87), HbA1c (MD = −0.26; 95% CI: −0.59~0.06; P = 0.11), and β2-MG (MD = −15.61; 95% CI: −32.95~1.73; P = 0.08). Conclusions This study indicates that JSB is an effective accessory therapeutic medicine for patients with early DN. It contributes to decreasing blood pressure and the content of triglyceride and improving the renal function of early DN patients. However, there is still a need to further verify the auxiliary therapeutic effect of JSB with more strictly designed RCTs with large sample and multiple centers in the future.