Effects of dietary leucine and valine levels on growth performance, glycolipid metabolism and immune response in Tilapia GIFT Oreochromis niloticus.

An 8-week feeding trial was performed to evaluate the effects of dietary leucine (Leu) and valine (Val) levels on growth performance, glycolipid metabolism and immune response in Oreochromis niloticus. Fish (15.23 ± 0.05 g) were randomly fed four diets containing two Leu levels (1.2% and 2.3%) and two Val levels (0.7% and 1.4%) as a 2 × 2 experimental design (LL-LV, LL-HV, HL-LV and HL-HV). Compared with LL-LV group, the growth parameters (final weight, daily growth coefficient (DGC) and growth rate per metabolic body weight (GRMBW)), feed conversion rate (FCR), the activities of intestinal amylase, lipase, creatine kinase (CK) and Na+, K+-ATPase, liver NAD+/NADH ratio, as well as the expression of SIRT1, GK, PK, FBPase, PPARα, CPT IA, ACO and IL10 all increased significantly in the HL-LV group; however, in the high Val group, final weight, DGC, GRMBW, intestinal enzyme activities, as well as the expression of PEPCK, SREBP1, FAS, IL8 and IL10 of the HL-HV group were significantly lower than those of the LL-HV group, while the opposite was true for the remaining indicators. Significant interactions between dietary Leu and Val were observed in final weight, DGC, GRMBW, plasma IL1ß and IL6 levels, intestinal amylase and CK activities, liver NAD+/NADH ratio, as well as the expression of SIRT1, PK, PEPCK, FBPase, SREBP1, FAS, PPARα, CPT IA, ACO, NF-κB1, IL1ß, IL6 and IL10. The highest values of growth parameters, intestinal enzyme activities and expression of SIRT1, FBPase, PPARα, CPT IA and ACO were observed in the HL-LV group, while the opposite was true for the expression of SREBP1, FAS, PPARα, NF-κB1, IL1ß and IL6. Overall, our findings indicated that dietary Leu and Val can effect interactively, and fish fed with diets containing 2.3% Leu with 0.7% Val had the best growth performance and hepatic health status of O. niloticus.

Effects of Astragalus Combined with Angelica on Bone Marrow Hematopoiesis Suppression Induced by Cyclophosphamide in Mice.

Danggui Buxue Tang (DBT), a combination of Astragalus and Angelica at a 5 : 1 ratio, mainly promotes hematopoiesis. However, in the clinic, the combination ratio of Astragalus and Angelica to treat low hematopoietic function is not an absolute 5 : 1 ratio, suggesting that the herbs may promote hematopoiesis better after being combined at a certain range of ratios. The objective of this study is to investigate the effect of different ratio combinations of Astragalus and Angelica on bone marrow hematopoiesis suppression induced by cyclophosphamide (CTX) and to probe the interaction and mechanism of Astragalus combined with Angelica in promoting hematopoiesis. Following establishment of the model, mice were administered with Astragalus (6.00 g·kg-1), Angelica (3.00 g·kg-1), and combinations of Astragalus and Angelica at different ratios, including 10 : 1 (Astragalus 9.81 g·kg-1+Angelica 0.98 g·kg-1), 5 : 1 (Astragalus 9.00 g·kg-1+Angelica 1.80 g·kg-1), 2 : 1 (Astragalus 7.71 g·kg-1+Angelica 3.08 g·kg-1), 1 : 1 (Astragalus 5.40 g·kg-1+Angelica 5.40 g·kg-1), 1 : 2.5 (Astragalus 3.08 g·kg-1+Angelica 7.71 g·kg-1), 1 : 5 (Astragalus 1.80 g·kg-1+Angelica 9.00 g·kg-1), and 1 : 10 (Astragalus 0.98 g·kg-1+Angelica 9.81 g·kg-1). Our results suggested that Astragalus mixed with Angelica synergistically promoted hematopoiesis best when the combination ratio of Astragalus and Angelica was 1 : 1, 1 : 2.5 or 1 : 5; moreover, the effect of Angelica was greater than that of Astragalus. The potential mechanisms of the combinations of Astragalus and Angelica that promote hematopoiesis include the dissolution of the effective components, promoting the synthesis and secretion of hematopoietic growth factor (HGF) and the proliferation of hematopoietic progenitor cells (HPCs).

[Effects of Astragali Radix combined with Angelicae Sinensis Radix on the proliferation of hematopoietic stem cells senescence model in mice].

The aim is to study the effect and its mechanism of Astragalus Radix combined with Angelicae Sinensis Radix on the proliferation of hematopoietic stem cells(HSCs) in senescence model. After drug-containing plasma of rats was prepared via intragastric administration, HSCs of mice were cultured in vitro, and then they were divided into blank control group, model group, blank plasma group, Astragalus Radix + Angelicae Sinensis Radix 1∶1 group and 10∶1 group, Angelicae Sinensis Radix plasma group, and Astragalus Radix plasma group. HSCs senescence model was induced by using tert-butyl hydrogen peroxide(t-BHP), and intervened by drug-containing plasma. Cells senescence rate was tested by SA-ß-galactosidase staining method; cell cycle distribution was determined by flow cytometry; Cyclin D1, P21, and P53 mRNA were measured with RT-PCR, and Cyclin D1 protein expression was measured by Western blot. Results showed that after being induced by t-BHP, senescence rate of HSCs was increased; cell proliferation ability was decreased; count of G0/G1 phase cells was increased; count of G2/M+S phase cells was reduced; Cyclin D1 expression was down-regulated while P53, P21 expression was up-regulated, which were reversed by Astragalus Radix + Angelicae Sinensis Radix 1∶1 and 10∶1, single Angelicae Sinensis Radix, and single Astragalus Radix plasma. Furthermore, the above effects were most obvious in Astragalus Radix+Angelicae Sinensis Radix 1∶1 group. These results suggested that t-BHP can promote HSCs senescence and reduce cell proliferation ability. Angelicae Sinensis Radix, Astragalus Radix and their combinations can inhibit HSCs senescence, promote HSCs proliferation as well as cell cycle conversion; moreover, the effects of 1∶1 Astragalus Radix+Angelicae Sinensis Radix were strongest. The mechanisms may be related to up-regulating the expression of cell cycle positive regulator, down-regulating the expression of cell cycle negative regulator, thus promoting the cells to enter the proliferation phase from the stationary phase.

[Effect of astragaloside â £ combined with Panax notoginseng saponins on cerebral ischemia-reperfusion injury and study of pharmacokinetics in rats].

The aim is to study the effect of astragaloside Ⅳ (AST Ⅳ) combined with Panax notoginseng saponins (PNS) on cerebral ischemia-reperfusion injury, and to probe the synergistic mechanism through the pharmacokinetics of the four major components such as AST Ⅳ, ginsenoside Rg1 (Rg1), ginsenoside Rb1 (Rb1), notoginsenoside R1 (R1) in cerebral ischemia-reperfusion rats. Following the establishment of cerebral ischemia/reperfusion model in rats by modified suture method, neurological function score, cerebral infarction area and pathomorphology were used to evaluate the pharmacological effect that the combination of AST Ⅳ and PNS antagonized cerebral ischemia-reperfusion injury; the contents of AST Ⅳ, Rg1, Rb1, R1 in rat plasma of different time points were determined with ultra performance liquid chromatography tandem massspectrometry (UPLC-MS/MS), pharmacokinetic parameters were calculated and pharmacokinetics changes of the main effective components were analyzed. The results showed that AST Ⅳ, PNS alone and their combination could reduce the cerebral infarction area of rats, relieve the behavioral scores of neurologic deficit, improve the pathological changes after cerebral ischemia, the effects of the combination were better. Among AST Ⅳ, Rg1, Rb1, R1, the area under the curve (AUC) was significantly increased, the mean residence time of (MRT0-t) was delayed, the peak concentration (Cmax) was significantly raised, the apparent volume of distribution (Vz/F) was reduced, and the clearance rate in vivo was significantly slowed. It suggested that AST Ⅳ combined with PNS has synergistic enhancement on anti-cerebral ischemia/reperfusion injury, moreover, make the pharmacokinetic behavior of the main effective components change, the mechanism may be associated with prolonging the retention time of the effective components in cerebral ischemia condition, elevating the bioavailability.

[The fluorescence characteristics of dissolved organic matter (DOM) in the seagrass ecosystem from Hainan by fluorescence excitation-emission matrix spectroscopy].

The fluorescence characteristics of dissolved organic matter (DOM) were determined in the seagrass ecosystem collected in Xincun Bay of Hainan Island in late January, 2013, using fluorescence excitation-emission matrix spectroscopy (EEMs). EEMs spectra showed 2 types of fluorescence signals in DOM samples, three hurnic-like fluorescence peaks and two protein-like fluorescence peaks, respectively. The former included UVC peak A (Ex/Em: 230/430 nm), UVA peak C (Ex/Em: 350/440 nm), and UVA peak M (Ex/Em: 300/380-400 nm), while the latter included tryptophan-like peaks R (Ex/Em: 230/355 - 375 nm) and N (Ex/Em: 280-300/365-380 nm). Peak N was more like a combination of Peak M and Peak R. Moreover, free tyrosine-like molecules in DOM from the seagrass-beds ecosystem did not exist because the tyrosine-like fluorescence was not found. There were significant positive correlations of peak N with M and R (0. 97 and 0. 54 for R2, respectively), and peak A with C (0. 86 for R2), showing their same sources and biogeochemical behaviors. The change law of mean fluorescence intensities of those fluorescence signals was R (0. 304 RU) >A (0. 194 RU) >M (0. 147 RU) >N (0. 125 RU) >C (0. 051 RU). And, higher . L-1 concentrations of all the fluorescence occurred in the coastal waters inshore, with low values in two small regions located in the southwest and southeast of the bay where the seagrasses flourished. The distributions of those fluorescence signals in Xincun Bay suggested that the dynamics responsible for the humic-like fluorescence might be the same as that responsible for the protein-like fluorescence. The high fluorescence index (FI: 1. 81), high biological index (BIX: 1. 44) and low humification index (HIXa: 4. 2 and HIXb: 0. 81) showed that the DOM from the seagrass-dominant ecosystem has a strong autochthonous contribution and poor humification degree. The results clearly suggested that the DOM in this region has a rather unique fluorescence characteristic and is quite different from other aquatic environments.

Corrigendum: Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: from static images to CEUS video analysis.

[This corrects the article DOI: 10.3389/fonc.2022.951973.].

Effects of borneol combined with astragaloside IV and Panax notoginseng saponins regulation of microglia polarization to promote neurogenesis after cerebral ischaemia.

OBJECTIVE: To study the effect of borneol combined with astragaloside IV and Panax notoginseng saponins (BAP) on promoting neurogenesis by regulating microglia polarization after cerebral ischaemia-reperfusion(CI/R) in rats. METHODS: A focal CI/R injury model was established. Evaluated the effects of BAP on ischaemic brain injury, on promoting neurogenesis, on inhibiting Inflammatory microenvironment and TLR4/MyD88/NFκB signalling pathway. A microglia oxygen-glucose deprivation reoxygenation (OGD/R) model was established that evaluated the effects of BAP on regulating the polarization of microglia and inflammatory microenvironment. RESULTS: BAP can inhibit the expression of TLR4, MyD88 and NFκB proteins, reduce IL-1ß and increase IL-10, reduce M1 type microglia and increase M2 microglia. The proliferation of neural stem cells increased, synaptic gap decreased, synaptic interface curvature increased, expression of SYN and PSD95 proteins increased, which improved the neurological dysfunction and reduced the volume of cerebellar infarction and nerve cell injury. CONCLUSION: BAP can reduce CI/R injury and promote neurogenesis, the effect is related to inhibition of the activation of TLR4/MyD88/NFκB, regulating the polarization of microglia from M1 type to M2 type and inhibition of inflammatory response.

Monomeric C-reactive protein evokes TCR Signaling-dependent bystander activation of CD4+ T cells.

Bystander activation of T cells is defined as induction of effector responses by innate cytokines in the absence of cognate antigens and independent of T cell receptor (TCR) signaling. Here we show that C-reactive protein (CRP), a soluble pattern-recognition receptor assembled noncovalently by five identical subunits, can instead trigger bystander activation of CD4 + T cells by evoking allosteric activation and spontaneous signaling of TCR in the absence of cognate antigens. The actions of CRP depend on pattern ligand-binding induced conformational changes that result in the generation of monomeric CRP (mCRP). mCRP binds cholesterol in plasma membranes of CD4 + T cells, thereby shifting the conformational equilibrium of TCR to the cholesterol-unbound, primed state. The spontaneous signaling of primed TCR leads to productive effector responses manifested by upregulation of surface activation markers and release of IFN-γ. Our results thus identify a novel mode of bystander T cell activation triggered by allosteric TCR signaling, and reveal an interesting paradigm wherein innate immune recognition of CRP transforms it to a direct activator that evokes immediate adaptive immune responses.

Astragalus extract alleviates nerve injury after cerebral ischemia by improving energy metabolism and inhibiting apoptosis.

This aim of this study was to explore the effects and molecular mechanisms of Astragalus extract against cerebral ischemia injury through the energy metabolism and apoptosis pathways of c­Jun N-terminal kinase (JNK) signal transduction. After the bilateral common carotid artery of C57BL/6 mice was occluded for 20 min followed by 1-h reperfusion, the ATP content, total adenine nucleotides (TAN), energy charge (EC), and sodium potassium ATPase (Na(+)-K(+)­ATPase) activity were decreased markedly in brain tissues. Astragalus extract markedly increased the ATP and ADP levels, EC value, and Na(+)-K(+)-ATPase activity. Twenty-four and 48 h after reperfusion, the neurocyte survival rate decreased and apoptosis rate increased, while the expression of phosphorylated JNK1/2, cytochrome c (Cyt C), and cysteine aspartic acid-specific protease (caspase)-9 and -3 were significantly enhanced in brain tissues. Astragalus extract significantly increased neurocyte survival and decreased the apoptosis rate as well as down-regulated the expression of p-JNK1/2, Cyt C, caspase-9, and caspase-3. These results suggest that Astragalus extract has neuroprotective effects against nerve injury after cerebral ischemia-reperfusion, and the underlying mechanism may be associated with improved cellular energy metabolism, inhibition of JNK signal transduction pathway activation, and then suppression of the mitochondrial apoptosis pathway.

Biopsy from the base and edge of gastric ulcer healing or complete healing may lead to detection of gastric cancer earlier: an 8 years endoscopic follow-up study.

BACKGROUND/AIMS: To assess the incidence of gastric cancer development in gastric benign ulcer patients and to evaluate the value of biopsy by taking specimens from both the base and edges of ulcers in contrast to the traditional biopsy which takes specimens from the edges of ulcers only. METHODOLOGY: An endoscopic followup of more than 1 year was conducted on 456 gastric ulcer patients in our hospital for a duration over 8 years. We collected clinical, endoscopic and pathological data and obtained at least 6 biopsies from both the edges and the bases of ulcers healing or complete healing, respectively and assessed H. pylori infection. RESULTS: Gastric cancers developed in 11 (2.41%) of 456 GU patients. In the experimental group, 3 cases that were diagnosed by histology showed adenocarcinoma with specimens taken from the ulcer bases and in the other 5 cases the specimens were taken from the ulcer edges. The detection rate of gastric cancer from gastric ulcer between experimental group and control group was statistically significant (4.57% vs. 1.07%, p<0.05). CONCLUSIONS: Gastric ulcer may develop into gastric cancer over a certain period of time in patients infected with H. pylori. Biopsies from ulcer bases and edges at the second or subsequent endoscopies may lead to defection of gastric cancer earlier and more effectively than the biopsies which take specimens from the edges of ulcers only.

[Effects of the combination of active component extracts from Astragalus membranaceus and Panax notoginseng on apoptosis, reactive oxygen species and mitochondrial membrane potential of PC12 cells with oxidative injury].

OBJECTIVE: To explore the effects and mechanisms of combining astragaloside IV (the effective component of Astragalus membranaceus) with notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1 (the effective components of Panax notoginseng) against oxidative injury in PC12 cells induced by cobalt chloride (CoCl2). METHODS: CoCl2 was used to stimulate PC12 cells to induce injury after transdifferentiation with nerve growth factor. Then the PC12 cells were divided into 10 groups and cultured with corresponding drugs. After culture, apoptotic cells were tested by using Hocchst 33258 fluorescent staining, the level of mitochondrial membrane potential (MMP) was analyzed by rhodamine 123 fluorescent staining and the content of reactive oxygen species (ROS) in PC12 cell was measured by dichlorofluorescin diacetate fluorescent staining. RESULTS: CoCl2 induced apoptosis along with the obvious decrease of MMP as well as overproduction of ROS in PC12 cells. Astragaloside IV, ginsenosides Rg1, ginsenosides Rb1 and notoginsenoside R1 had inhibition effects in different degree on PC12 cell apoptosis induced by CoCl2, reduced the overproduction of ROS and the decrease of MMP. The effects of the combination were better than those of active component alone. CONCLUSION: Active components extracted from Astragalus and Panax notoginseng can inhibit PC12 cell apoptosis induced by oxidative injury, furthermore, the effects were enhanced by combination of these components, which may be associated with jointly antagonizing the generation of ROS and raising MMP.

Neck and mediastinal hematoma caused by a foreign body in the esophagus with diagnostic difficulties: A case report.

BACKGROUND: Esophageal foreign body (FB) is a common clinical emergency. Clinically, computed tomography (CT) scans are important in the diagnosis of FBs in the esophagus. Here, we report a case of esophageal perforation and cervical hematoma, caused by a FB, whose uniqueness made rapid diagnosis difficult. CASE SUMMARY: A 42-year-old man was transferred to our hospital with esophageal perforation, which was accompanied by cervical and mediastinal hematoma. CT scans only revealed a black shadow, approximately 2.5 cm in diameter, in the upper esophagus. After multidisciplinary discussion, he was quickly subjected to mediastinal hematoma resection, peripheral nerve compression release, esophageal FB removal and esophagectomy. Eventually, we removed a small crab with a pointed tip from his esophagus. CONCLUSION: This was an unusual case of occurrence of sharp polygonal esophageal FBs caused by a small crab. Rapid diagnosis of this FB was difficult, mainly due to its translucent nature. Occurrence of sharp FBs, with cavities that sometimes only appear as black shadows on CT scans, can easily be mistaken for esophageal lumens. More attention should be paid to such sharp polygonal FBs.

Cholesterol-binding sequence is a key regulatory motif of cellular folding and conformational activation for C-reactive protein.

Human, rat, and mouse C-reactive protein (CRP) possess distinct expression patterns, but have similar conformations and conserved in vivo functions. We have previously demonstrated that this level-function mismatch is delicately tuned by the hidden activities of unfolded CRP. The cholesterol-binding sequence (CBS; a.a. 35-47) is a major functional motif exposed on monomeric CRP, which is the unfolded and activated conformation of CRP. We replaced the CBS of rat CRP with that of either mouse or human CRP, yielding two grafting mutants with unaffected pentameric assembly. However, these mutants exhibited altered cellular foldability and conformational activation efficiency that matched those of the CRP that provided the grafted CBS. These results indicate that CBS is a critical regulatory motif, whose variation maintains the pentameric assembly of CRP but derives distinct cellular foldabilities and conformational activation efficiencies, therefore helping to ensure that CRPs with various expression patterns exhibit overall conserved functions.

Purification of Recombinant Mouse C-Reactive Protein from Pichia Pastoris GS115 by Nickel Chelating Sepharose Fast-Flow Affinity Chromatography and P-Aminophenyl Phosphoryl Choline Agarose Resin Affinity Chromatography in Tandem.

C-reactive protein (CRP) is a circulating marker of inflammation yet with ill-defined biological functions. This is partly due to the uncharacterized activities of endogenous CRP in mice, the major animal model used to define protein function. The hurdles for purification and characterization of mouse CRP are its low circulating levels and the lack of specific antibodies. To clear these hurdles, here we developed an efficient expression system by constructing recombinant Pichia pastoris cells for secretion of native conformation mouse CRP. The recombinant expression of mouse CRP in Escherichia coli failed to yield sufficient amount of native protein, reflecting the importance of post-translational modification of glycosylation in aiding proper folding. By contrast, sufficient amount of native mouse CRP was successfully purified from P. pastoris. Preliminary purification was performed by Nickel Chelating Sepharose Fast-Flow affinity chromatography with 6 × His tags attached to the protein. Subsequently, p-Aminophenyl Phosphoryl Choline Agarose resin affinity chromatography was used for tandem purification. The purified mouse CRP showed native pentamer and capabilities of PC binding. Moreover, the 6 × His tag provides a convenient tool for detecting the interactions of mouse CRP with ligands.

Borneol enhances the protective effect against cerebral ischemia/reperfusion injury by promoting the access of astragaloside IV and the components of Panax notoginseng saponins into the brain.

BACKGROUND: Astragalus and Panax notoginseng are significant traditional Chinese medicines for treating ischemic stroke, with astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) being the major effective compounds, respectively. These compounds can also be used in combination. We have previously shown that AST IV and PNS have an antagonistic effect on cerebral ischemia/reperfusion (I/R) injury, and the combination of these two drugs can elevate this effect; unfortunately, AST IV and PNS cannot easily enter the brain tissues through the blood brain barrier (BBB). Previous studies have confirmed that the combination of borneol with other agents could promote the penetration of the drug components through the BBB. However, it remains unclear whether borneol can promote entry of the active components of AST IV and PNS into the brain tissues and enhance their effect against cerebral ischemia. OBJECTIVE: This study aimed to investigate the effects of a combination of borneol with AST IV and PNS against I/R injury and explore the mechanisms of borneol-promoting penetration of drug components into the BBB based on the drug transport of brain tissues. METHODS: A rat model of focal cerebral I/R injury was established, and drugs, including borneol, AST IV, and PNS, as well as their combinations were intragastrically administered. Subsequently, drug efficacy was assessed, and the condition of AST IV and PNS active components (Rg1, Rb1, R1) delivered into the brain was analyzed. Moreover, BBB permeability was determined, and the expression of related drug transporters and their genes were evaluated. RESULTS: After treatment with borneol, AST IV, PNS, AST Ⅳ+PNS, and borneol+AST Ⅳ+PNS after cerebral I/R, the neurological function deficit scores, cerebral infarct rate, and brain water content markedly decreased. The effects of the three-drug-combination were better than those of the drugs used alone and those of AST Ⅳ+PNS. Moreover, after I/R in rats, AST IV and the components of PNS (Rg1, Rb1, R1) were mainly found in the cerebral cortex and in the cerebellum, respectively, when used alone. Borneol combined with AST IV and PNS increased the contents of AST IV, Rb1, Rg1, and R1 in the cerebral cortex and in the cerebellum, thus, promoting the enrichment of active components to the cerebral cortex, especially to the affected side. In addition, following I/R, diffuse distribution of lanthanum particles in the basement membrane, intercellular and intracellular locations of rat brain tissues indicated BBB destruction and increase in permeability, which were alleviated in each drug group. The effects of borneol combined with AST IV and PNS were stronger than those of the drug single-used and those of the AST IV+PNS group. Finally, the expression of effluent transporters (ET) and their genes, including P-glycoprotein (P-gp), multidrug resistance protein (MRP)-1, MRP-2, MRP-4, and MRP-5 in brain tissues, strikingly increased after I/R. Borneol remarkedly down-regulated the protein expression of P-gp, MRP-2, and MRP-4 in the brain, whereas PNS down-regulated MRP-4 and MRP-5 protein expression. AST IV, AST IV+PNS, and bornoel+AST IV+PNS effectively decreased the expression of P-gp, MRP-2, MRP-4, and MRP-5 proteins. The effects of the three-drug combination were significantly greater than those of the drug single-used and AST IV+PNS groups. The expression of each ET gene manifested corresponding results. Meanwhile, PNS, AST IV+PNS, and bornoel+AST IV+PNS significantly inhibited the down-regulation of the uptake transporter organic anion transporting polypeptide (OATP)-2 expression, and the effect of bornoel+AST IV+PNS was stronger than that of other groups. CONCLUSION: After I/R, the brain tissues were injured, BBB permeability increased, expression of critical ET and their genes were markedly up-regulated, and the main uptake transporters were down-regulated. We propose that the combination of borneol, AST IV and PNS could enhance the effect against cerebral I/R injury and protect BBB integrity. The potential mechanism might be the delivery of AST IV and active components of PNS to the brain tissues after treatment in combination with borneol, which could be effectively promoted by down-regulating the expression of ETs and up-regulating the expression of uptake transporters in the brain tissues. This study was the first to demonstrate that borneol combined with AST IV+PNS enhanced the effect against cerebral I/R injury through promoting the entry of AST and PNS active components to the brain tissues. Thus, this study proposes an instructive role in developing effective active ingredients combination of Chinese medicine with clear ingredients and synergistic effects in terms of the characteristic of borneol.

Secretory quality control constrains functional selection-associated protein structure innovation.

Biophysical models suggest a dominant role of structural over functional constraints in shaping protein evolution. Selection on structural constraints is linked closely to expression levels of proteins, which together with structure-associated activities determine in vivo functions of proteins. Here we show that despite the up to two orders of magnitude differences in levels of C-reactive protein (CRP) in distinct species, the in vivo functions of CRP are paradoxically conserved. Such a pronounced level-function mismatch cannot be explained by activities associated with the conserved native structure, but is coupled to hidden activities associated with the unfolded, activated conformation. This is not the result of selection on structural constraints like foldability and stability, but is achieved by folding determinants-mediated functional selection that keeps a confined carrier structure to pass the stringent eukaryotic quality control on secretion. Further analysis suggests a folding threshold model which may partly explain the mismatch between the vast sequence space and the limited structure space of proteins.

Ultrasound-based radiomics analysis for differentiating benign and malignant breast lesions: From static images to CEUS video analysis.

Background: Continuous contrast-enhanced ultrasound (CEUS) video is a challenging direction for radiomics research. We aimed to evaluate machine learning (ML) approaches with radiomics combined with the XGBoost model and a convolutional neural network (CNN) for discriminating between benign and malignant lesions in CEUS videos with a duration of more than 1 min. Methods: We gathered breast CEUS videos of 109 benign and 81 malignant tumors from two centers. Radiomics combined with the XGBoost model and a CNN was used to classify the breast lesions on the CEUS videos. The lesions were manually segmented by one radiologist. Radiomics combined with the XGBoost model was conducted with a variety of data sampling methods. The CNN used pretrained 3D residual network (ResNet) models with 18, 34, 50, and 101 layers. The machine interpretations were compared with prospective interpretations by two radiologists. Breast biopsies or pathological examinations were used as the reference standard. Areas under the receiver operating curves (AUCs) were used to compare the diagnostic performance of the models. Results: The CNN model achieved the best AUC of 0.84 on the test cohort with the 3D-ResNet-50 model. The radiomics model obtained AUCs between 0.65 and 0.75. Radiologists 1 and 2 had AUCs of 0.75 and 0.70, respectively. Conclusions: The 3D-ResNet-50 model was superior to the radiomics combined with the XGBoost model in classifying enhanced lesions as benign or malignant on CEUS videos. The CNN model was superior to the radiologists, and the radiomics model performance was close to the performance of the radiologists.

Traceability of the geographical origin of Siraitia grosvenorii based on multielement contents coupled with chemometric techniques.

Siraitia grosvenorii (LHG) is widely used as a medicinal and edible material around the world. The objective of this study was to develop an effective method for the authentication of the geographical origin of LHG in its main producing area Guangxi, China, which is identified as Chinese Protected Designation of Origin product, against other producing regions in China. The content of 14 elements (K, Na, Ca, P, Mg, Al, B, Ba, Cu, Fe, Mn, Ni, Zn, and Sr) of 114 LHG samples was determined by inductively coupled plasma optical emission spectrometry. Multivariate analysis was then performed to classify the geographical origin of LHG samples. The contents of multielement display an obvious trend of clustering according to the geographical origin of LHG samples based on radar plot and principal component analysis. Finally, three supervised statistical techniques, including linear discriminant analysis (LDA), k-nearest neighbours (k-NN), and support vector machine (SVM), were applied to develop classification models. Finally, 40 unknown LHG samples were used to evaluate the predictive ability of model and discrimination rate of 100%, 97.5% and 100% were obtained for LDA, k-NN, and SVM, respectively. This study indicated that it is feasible to attribute unknown LHG samples to its geographical origin based on its multielement content coupled with chemometric techniques.

Molecular characterization of thioredoxin-interacting protein (TXNIP) from Megalobrama amblycephala and its potential roles in high glucose-induced inflammatory response.

This study aimed to characterize the full-length cDNA of thioredoxin-interacting protein (TXNIP) from Megalobrama amblycephala, and investigate its roles in high glucose (HC)-induced inflammatory response. The cDNA obtained covered 2706-bp with an open reading frame of 1203-bp encoding 400 amino acids, compared to Cyprinus carpio, it showed 89.96% homology. The highest expression of txnip was observed in head kidney followed by spleen and liver. After a 12-week feeding trial, high-carbohydrate diet remarkably increased txnip expression in liver and white muscle. Glucose administration resulted in a remarkably increased liver txnip expression, which peaked at 1 h. Thereafter, the expression decreased remarkably to the basal value at 12 h. However, insulin injection resulted in a significant decrease in txnip expression with minimum values attained at 2 h. Subsequently, it gradually increased to the normal values. Moreover, in the in-vitro study, over-expression of txnip along with remarkably increased il-1ß and il-6 expression in hepatocytes, and its knockdown led to remarkably reduced il-1ß expression. Furthermore, metformin treatment remarkably increased the cell viability and trx expression of hepatocytes under high glucose, while the opposite was true for ROS levels, LDH activity, the ALT/AST ratio, Txnip protein content and the transcriptions of txnip, tnfα and il-1ß.