The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

This study selected the top five general hospitals in the United States of America, collected the practice information of acupuncturists through the official website, and analyzed the professional department, expertise, professional title, education background, residency, fellowship, board certification, etc. of these acupuncturists to understand the practice situation of acupuncturists in the hospitals. The results of the study showed the practice of acupuncturists in the United States of America is improving. With further localization, locally trained acupuncturists have gradually become the main body of acupuncturists; acupuncture treatment is still mainly for analgesia, but the scope of treatment continues to expand, and departments that accept acupuncturists are gradually increasing. However, the group of licensed acupuncturists is still a minority in the group of acupuncturists in the United States of America. Native American physicians still use acupuncture as an alternative option and neglect to obtain a license. The entry barrier for acupuncturists still needs to be raised.

As an active hydroxyanthraquinone ingredient, emodin is abundant in Chinese medicine herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum.Modern pharmacological studies have shown that emodin has a variety of pharmacological activities including anti-tumor, anti-inflammatory and immunoregulatory, antibacterial and anti-viral effects, myocardial protection, neuroprotection, renal protection, bone protection, antifibrosis and so on, which indicate its high medicinal value and broad application prospects.This article aims to summarize the progress in the pharmacological activity and mechanism of action of emodin published in domestic and international journals over the last 5 years and highlight the potential targets and molecular signaling pathways linked with emodin, so as to provide some clues and references for further development and clinical application of emodin.

Objective To investigate the impacts of midazolam on the proliferation,migration and invasion of breast cancer MDA-MD-231 cells and its regulation on cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element binding protein(CREB)signaling pathway.Methods MDA-MD-231 cells were cultured in vitro and grouped into control group,midazolam L group,midazolam M group,midazolam H group,and midazolam H+Sp-cAMPS group.Midazolam L group,midazolam M group,midazolam H group were treated with 5μmol/L,10μmol/L,and 20μmol/L of midazolam,respectively,midazolam H+Sp-cAMPS group was added with 20μmol/L of midazolam+10μmol/L of Sp-cAMPS 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay was applied to detect cell proliferation;The migration ability was detected by cell scratch test;Transwell test was applied to determine the invasion ability of cells;Cell apoptosis was detected by flow cytometry;The expression level of cAMP was detected by enzyme-linked immunosorbent assay(ELISA);Western blot was applied to verify the expression of phosphorylated(p-)PKA/PKA,p-CREB/CREB protein.Results Compared with control group,the cells in midazolam L group,midazolam M group,midazolam H group showed apoptosis,the apoptosis rate was obviously increased,the cell proliferation,migration and invasion abilities and the expression levels of cAMP,p-PKA/PKA,p-CREB/CREB proteins were obviously decreased(P<0.05);Compared with midazolam H group,midazolam H+Sp-cAMPS group had good cell growth,obviously reduced apoptosis rate,and obviously increased cell proliferation,migration and invasion abilities,and the expression levels of cAMP,p-PKA/PKA,p-CREB/CREB proteins(P<0.05).Conclusion Midazolam may inhibit the proliferation,migration and invasion of breast cancer cells by inhibiting the activation of cAMP/PKA/CREB signaling pathway.

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K _d value of 0.11 μmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

Background music has been increasingly affecting people's lives. The research on the influence of background music on working memory has become a hot topic in brain science. In this paper, an improved electroencephalography (EEG) experiment based on n-back paradigm was designed. Fifteen university students without musical training were randomly selected to participate in the experiment, and their behavioral data and the EEG data were collected synchronously in order to explore the influence of different types of background music on spatial positioning cognition working memory. The exact low-resolution brain tomography algorithm (eLORETA) was applied to localize the EEG sources and the cross-correlation method was used to construct the cortical brain function networks based on the EEG source signals. Then the characteristics of the networks under different conditions were analyzed and compared to study the effects of background music on people's working memory. The results showed that the difference of peak periods after stimulated by different types of background music were mainly distributed in the signals of occipital lobe and temporal lobe ( < 0.05). The analysis results showed that the brain connectivity under the condition with background music were stronger than those under the condition without music. The connectivities in the right occipital and temporal lobes under the condition of rock music were significantly higher than those under the condition of classical music. The node degrees, the betweenness centrality and the clustering coefficients under the condition without music were lower than those under the condition with background music. The node degrees and clustering coefficients under the condition of classical music were lower than those under the condition of rock music. It indicates that music stimulation increases the brain activity and has an impact on the working memory, and the effect of rock music is more remarkable than that of classical music. The behavioral data showed that the response accuracy in the state of no music, classical music and rock music were 86.09% ± 0.090%, 80.96% ± 0.960% and 79.36% ± 0.360%, respectively. We conclude that background music has a negative impact on the working memory, for it takes up the cognitive resources and reduces the cognitive ability of spatial location.
Brain ; Cognition ; Electroencephalography ; Humans ; Memory, Short-Term ; Music

Lung nodules are the main manifestation of early lung cancer. So accurate detection of lung nodules is of great significance for early diagnosis and treatment of lung cancer. However, the rapid and accurate detection of pulmonary nodules is a challenging task due to the complex background, large detection range of pulmonary computed tomography (CT) images and the different sizes and shapes of pulmonary nodules. Therefore, this paper proposes a multi-scale feature fusion algorithm for the automatic detection of pulmonary nodules to achieve accurate detection of pulmonary nodules. Firstly, a three-layer modular lung nodule detection model was designed on the deep convolutional network (VGG16) for large-scale image recognition. The first-tier module of the network is used to extract the features of pulmonary nodules in CT images and roughly estimate the location of pulmonary nodules. Then the second-tier module of the network is used to fuse multi-scale image features to further enhance the details of pulmonary nodules. The third-tier module of the network was fused to analyze the features of the first-tier and the second-tier module of the network, and the candidate box of pulmonary nodules in multi-scale was obtained. Finally, the candidate box of pulmonary nodules under multi-scale was analyzed with the method of non-maximum suppression, and the final location of pulmonary nodules was obtained. The algorithm is validated by the data of pulmonary nodules on LIDC-IDRI common data set. The average detection accuracy is 90.9%.

Objective To systematically evaluate the biomechanical recovery of drilled holes in the femur in SD rats.Methods Eighteen female SD rats were randomized into 3 even groups (n =6).Models of 2-mm drilled holes in bilateral femurs were established in groups A and B with 2 holes on each side while no drilling was performed in group C.Samples were harvested in group A at postoperative 4 weeks,in group B at postoperative 8 weeks while at both 4 and 8 weeks in group C.The samples were evaluated in terms of linear elasticity (compression test),viscoelasticity (relaxation and creep tests) and durability (fatigue failure test).Micro-CT scan was performed to measure the bone volume fraction (BV/TV) and bone mineral density (BMD) of new bone.Sirus red staining was performed to measure regeneration of type Ⅰ collagen of new bone.Results The elasticity modulus,maximum load,compression strength and conditional yield limit in groups A were significantly lower than those in group B which were also significantly lower than those in group C (P ＜ 0.05).At 7,200 s,the relaxation (14.56 ±0.69 MPa) and creep variation (11.37％ ± 0.70％) in group A were significantly higher than those in group B (11.06 0.63 MPa and 8.98％ ± 0.40％) which were also significantly higher than those in group C (6.99 ±0.56 MPa and 5.10％ ±0.23％) (P ＜ 0.05).At the constant amplitude loads from 20 N to 200 N,from 20 N to 300 N and from 20 N to 400 N,the recycling numbers in group A (6,044.3 ±879.7,4,093.3 ±628.5 and 1,919.3 ±847.5) were significantly lower than those in group B (10,192.3 ± 1,109.1,6,750.6 ± 818.0 and 3,376.6 ± 671.3) which were also significantly lower than those in group C (28,068.3 ±2,702.6,11,788.3 ± 1,141.6 and 5,296.3 ± 735.0) (P ＜ 0.05).By micro-CT scan,the BVT and BMD in group A were significantly lower than those in group B which were also significantly lower than those in group C (P ＜ 0.05).The sirus red staining showed the type Ⅰ collagen in the bone defect area was completely regenerated in group B.Conclusion Systematic biomechanical measurements may actually detect the characteristics of biomechanical recovery of bone holes in SD rats,enriching the basic research on the bone damage repairing progress.