Swine acute diarrhea syndrome coronavirus Nsp1 suppresses IFN-λ1 production by degrading IRF1 via ubiquitin-proteasome pathway.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus that causes acute watery diarrhea, vomiting, and dehydration in newborn piglets. The type III interferon (IFN-λ) response serves as the primary defense against viruses that replicate in intestinal epithelial cells. However, there is currently no information available on how SADS-CoV modulates the production of IFN-λ. In this study, we utilized IPI-FX cells (a cell line of porcine ileum epithelium) as an in vitro model to investigate the potential immune evasion strategies employed by SADS-CoV against the IFN-λ response. Our results showed that SADS-CoV infection suppressed the production of IFN-λ1 induced by poly(I:C). Through screening SADS-CoV-encoded proteins, nsp1, nsp5, nsp10, nsp12, nsp16, E, S1, and S2 were identified as antagonists of IFN-λ1 production. Specifically, SADS-CoV nsp1 impeded the activation of the IFN-λ1 promoter mediated by MAVS, TBK1, IKKε, and IRF1. Both SADS-CoV and nsp1 obstructed poly(I:C)-induced nuclear translocation of IRF1. Moreover, SADS-CoV nsp1 degraded IRF1 via the ubiquitin-mediated proteasome pathway without interacting with it. Overall, our study provides the first evidence that SADS-CoV inhibits the type III IFN response, shedding light on the molecular mechanisms employed by SADS-CoV to evade the host immune response.

A one-step process for multi-gradient wettability modification on a polymer surface.

The surface modification technique is applied in microfluidic devices to modify wettability and achieve different flow velocities. Currently available methods for poly(dimethylsiloxane) (PDMS) surfaces may reliably induce wettability changes, but only one area can be altered at a time. This work introduces the controlled gradient oxygen plasma modification (CGPM) technique, which layers several resin masks with varying porosities on top of the PDMS surface. Selective wettability of the PDMS surface can be achieved by varying the oxygen plasma density above the modified material's surface by manipulation of the porosity value. Through the implementation of the COMSOL plasma module, the impact of the mask's porosity, through-hole size, distribution, and distance from the PDMS surface on wettability was studied. The suggested CGPM approach was characterized by contact angle measurements. During the 25-second CGPM procedure, the PDMS surface's contact angle continually changed from 8.77° to 76.98°. An integrated microfluidic device was created and manufactured to identify D-dimers to illustrate this method. In comparison with standard oxygen plasma treatment, the D-dimer assay was finished in 10 minutes and had a dynamic range of 1-1000 ng mL-1, with a peak fluorescence signal augmentation of 78.3% and an average fluorescence intensity enhancement of 31.1%.

Relationship between plasma amino acid and carnitine levels and primary angle-closure glaucoma based on mass spectrometry metabolomics.

World blindness is primarily caused by glaucoma. It has been predicted that by 2040, 118 million individuals will have glaucoma. Among Asians and Africans, primary angle-closure glaucoma (PACG) is the most prevalent type of glaucoma, for which treatment options are currently very limited. At present, lowering intraocular pressure (IOP) is the primary approach for PACG treatment. However, some PACG patients with decreased IOP measurements still advance. Additionally, because of the complicated pathophysiology, there are no biomarkers for diagnosis. Metabolomics is the study of the metabolites produced by all cellular processes in a biological sample, providing a method for identifying biomarkers and early diagnosis. Nevertheless, metabolomics has infrequently been applied to PACG. Previous research conducted by our lab on plasma metabolite fatty acids in PACG patients revealed reduced free fatty acid (FFA) levels, which may be connected to lipid peroxidation. To ascertain the relationship between other metabolites and PACG. We compared levels of amino acids and carnitine in patients with PACG (n = 147) and non-glaucoma (n = 340). Using metabolomics analysis, twenty-one amino acids and twenty-six carnitines (a total of ninety-six indicators) were examined. Odds ratios (OR) and 95% confidence intervals (CI) for these metabolites in relation to PACG were calculated. The relationship between ocular measures and metabolites was assessed by Spearman's rank correlation. Predictive performance was evaluated using the receiver operating characteristic (ROC). The C8/C2 level was comparable across patients with PACG and individuals without glaucoma based on the Wilcoxon rank-sum test. The PACG group had lower levels of Arginine (Arg), Ornithine (Orn), Arg/Orn, Orn/Cit, and C26/C20 than the nonglaucoma group, whereas Cit/Arg and C4/C2 ratios were greater. Both univariate and multivariate models showed a negative correlation between Orn and Orn/Cit and PACG. In the univariate model, palmitoylcarnitine (C16) had a negative correlation with PACG. According to our findings, metabolic profiles of plasma amino acids and carnitine between PACG patients and controls are different. The combination of amino acids and carnitine increased the predictive value of PACG. The Orn and Arg were negatively correlated with the local ocular neurodegenerative pathology. We speculate lipid peroxidation may explain the reduction in C16, and the decrease in Orn may be associated with hyperammonia neurotoxicity.

Activating transcription factor 4 in erythroid development and [Formula: see text]-thalassemia: a powerful regulator with therapeutic potential.

Activating transcription factor 4 (ATF4) is a fundamental basic region/leucine zipper transcription factor, responds to various stress signals, and plays crucial roles in normal metabolic and stress response processes. Although its functions in human health and disease are not completely understood, compelling evidence underscores ATF4 is indispensable for multiple stages and lineages of erythroid development, including the regulation of fetal liver hematopoietic stem cells, induction of terminal erythroid differentiation, and maintenance of erythroid homeostasis. [Formula: see text]-Thalassemia is a blood disorder arising from mutations in the [Formula: see text]-globin gene. Reactivating the expression of the [Formula: see text]-globin gene in adult patients has emerged as a promising therapeutic strategy for ameliorating clinical symptoms associated with [Formula: see text]-thalassemia. Recent research has suggested that ATF4 contributes to decreased fetal hemoglobin (HbF) level through its binding to potent negative regulators of HbF, such as BCL11A and MYB. Notably, evidence also suggests a contrasting outcome where increased ATF4 protein levels are associated with enhanced HbF at the transcriptional level. Consequently, the identification of mechanisms that modulate ATF4-mediated [Formula: see text]-globin transcription and its effects on erythroid development may unveil novel targets for [Formula: see text]-thalassemia treatment.

Composite Microfluidic Petri Dish-Chip (MPD-Chip) without Protein Coating for 2D Cell Culture.

Hydrophilicity is a requisite attribute for the 2D cell culture substrate's surface, facilitating cell adhesion and spreading. Conventional poly(dimethylsiloxane) (PDMS) microfluidic chips necessitate protein coatings to enhance hydrophilicity; however, this approach is afflicted by issues of transient efficacy, interference with cell analysis, and high costs. This paper presents a protein-free microfluidic chip, termed a "microfluidic Petri dish-chip (MPD-chip)", integrating PDMS as the cover and a tissue culture-treated (TC-treated) Petri dish as the substrate. Microstructures are hot-embossed onto the Petri dish substrate using a silicon mold. This meticulous replication process serves to establish stable flow field dynamics within the chip. A simplified method for irreversible bonding, utilizing plasma activation and silylation, is proposed for affixing the PDMS cover onto the microstructured Petri dish substrate. The prepared composite chip exhibits remarkable tightness, boasting a notable bond strength of 2825 kPa. Furthermore, the composite microfluidic chip demonstrates the capability to withstand flow velocities of at least 200 µL/min, effectively meeting the required injection standards for both cell suspension and culture medium. SH-SY5Y and HeLa cells are cultured dynamically in the MPD-chip and control groups. Outcomes encompassing normalized cell density, cell adhesion area, and cell viability metrics unequivocally highlight the superiority of the MPD-chip in facilitating long-term two-dimensional (2D) cell cultures.

Curcumin Induces Apoptosis by Suppressing XRCC4 Expression in Hepatocellular Carcinoma.

Curcumin is a chemical with various pharmacological activities used for cancer treatment. It inhibits hepatocellular carcinoma (HCC) by inducing apoptosis. Here, the mechanism underlying the effect of curcumin on the apoptosis of HCC cells was studied. Cell counting kit-8 and plate cloning assays were used to assess the proliferation of HCC cells, and acridine orange/ethidium bromide and Annexin V/PI staining were used to analyze their apoptosis. HCC xenograft tumor models were established to validate anti-cancer effects of curcumin. Expression levels of XRCC4 protein in tumor tissues were assessed by immunohistochemistry. Correlation between XRCC4 expression and the prognosis of patients with HCC was analyzed by integrating publicly available gene expression data. Curcumin inhibited HCC cells proliferation in a dose-dependent manner. Compared with the control group, curcumin significantly promoted the apoptosis of HCC cells in vitro and in vivo. Immunohistochemical analysis revealed that curcumin downregulated XRCC4 expression levels in HCC tissues. Prognosis of HCC patients with high XRCC4 expression was poorer than that of patients with low XRCC4 expression. Therefore, curcumin exerts anti-cancer effects by inhibiting cell proliferation and promoting cell apoptosis in HCC. This may be due to curcumin interference in the repair process of the nonhomologous DNA terminal link of HCC cells by downregulating XRCC4 expression.

A microfluidic device inspired by leaky tumor vessels for hematogenous metastasis mechanism research.

Endothelial intercellular pores of tumor vessels generally lead to enhanced interstitial flow and may facilitate the migration of tumor cells. The permeability of tumor vessels causes a concentration gradient of growth factors (CGGF) from blood vessels to tumor tissues, which is opposite to the direction of interstitial flow. In this work, exogenous chemotaxis under the CGGF is demonstrated as a mechanism of hematogenous metastasis. A bionic microfluidic device inspired by endothelial intercellular pores of tumor vessels has been designed to study the mechanism. A porous membrane vertically integrated into the device using a novel compound mold is utilized to mimic the leaky vascular wall. The formation mechanism of the CGGF caused by endothelial intercellular pores is numerically analyzed and experimentally verified. The migration behavior of U-2OS cells is studied in the microfluidic device. The device is divided into three regions of interest (ROI): primary site, migration zone, and tumor vessel. The number of cells in the migration zone increases significantly under the CGGF, but decreases under no CGGF, indicating tumor cells may be guided to the vascellum by exogenous chemotaxis. Transendothelial migration is subsequently monitored, demonstrating the successful replication of the key steps in vitro in the metastatic cascade by the bionic microfluidic device.

The formation mechanism of the precursor film in high temperature molten metal systems: insight into structural disjoining pressure.

A precursor film is a unique microfluidic entity that arises at the liquid/solid interface. The formation mechanism of this entity in high-temperature systems is yet to be explained, mainly due to the limitations posed by the increased reaction at the solid/liquid interface. In this study, we investigate the formation process of the precursor film in high-temperature molten metal systems (Ag/Ni, Au/Ni, and Cu/Ni) using molecular dynamics simulations. The alloying energies for different alloying pairs were determined to extract the excess energy, which was found to be distributed from the interface to the upper liquid. The pattern of this energy distribution determines the shape of the near-surface liquid, including the precursor film. This relationship is further reflected by the structural disjoining pressure, which is the excess pressure exerted by the ordered microstructures within the wedge-shaped area of the droplet. Strong nonlinearity has been found in the structural disjoining pressure of Ag/Ni and Au/Ni systems, which is considered to be the main reason for the formation of the precursor film. The fluctuation of the dissolution rate is also reflected in the disjoining pressure, and the inhibition of dissolution on the precursor film formation is phenomenally clarified.

Activated cell-cycle CDK4/CyclinD1-pRB-E2F1 signaling pathway is involved in the apoptosis of dorsal raphe nucleus in the rat model of PTSD.

Dysregulation of the dorsal raphe nucleus (DRN) has been revealed to contribute to cognitive and arousal impairments associated with post-traumatic stress disorder (PTSD) in an animal model. In our research an acute exposure to single prolonged stress (SPS) was used to establish PTSD rat model and the effects related to cell-cycle signaling pathway in DRN were examined. Apoptosis in DRN was detected by TUNEL staining, showing that DRN apoptosis number was sharply increased after SPS. SPS triggered cell-cycle CDK4/CyclinD1-pRB-E2F1 signal pathway. Treatment with CDK4 inhibitor Abemaciclib successfully attenuated the DRN apoptosis and rescued decreased spatial learning and memory abilities in SPS rats, indicating that activation of CDK4/CyclinD1-pRB-E2F1 pathway was involved in DRN apoptosis, which may be one of the pathogenesis for PTSD.

Permeation-Enhanced Degassing Method Based on Xylem Embolism Repair and Gas Permeable Materials.

Microfluidic devices have developed a wide range of applications in the fields of biomedicine, chemistry, and analytical science. But it is easy to form and accumulate bubbles in microfluidic devices. These bubbles could decrease the detection sensitivity, cause inaccurate analysis results, and even damage the functional region of the device. Inspired by the embolism repair mechanism of angiosperms and the permeability of gas permeable materials, this work proposes a bioinspired permeation-enhanced degassing method. Bionic redundant pits are used in this method to keep bubbles from spreading between microchannels and maintain the continuity of the flow. A hydrophobic gas permeable material is used to enhance the bubble capture capability and accelerate the degassing process. This method can eliminate bubbles automatically and continuously in real time without auxiliary equipment. Compared to the bubble removal only depending on solution in water, the degassing effect of the permeation-enhanced degassing method shows about 1.6 times improvement in the same conditions, and the capability of trapping bubbles is improved by 1.33 times. In this paper, this method was integrated into a concentration gradient generator and a cell culture device. The results show that the concentration gradient generator with degassing structures can dissolve bubbles in a rapid way and reach the stability of the concentration gradient within 5-15 min. The degassing method can run for a long time and improve the cell density and cell viability of HeLa cells up to 2.64 and 1.12 times, respectively. The method has a broad application prospect in microfluidic fields including biomedical fluid processing, virus detection, and microscale reactor operation.

Ablation of Immunoproteasome ß5i Subunit Suppresses Hypertensive Retinopathy by Blocking ATRAP Degradation in Mice.

Inflammation is associated with retinal diseases. Our recent data demonstrate that immunoproteasome catalytic subunit ß2i contributes to angiotensin II (Ang II)-induced retinopathy in mice. Here, we investigated the role of another catalytic subunit ß5i in regulating retinopathy and its underlying mechanisms. We induced a murine model of retinopathy by infusing Ang II (3,000 ng/kg/min) for 3 weeks into wild-type (WT) mice, ß5i-knockout (KO) mice, or WT mice injected with either adenovirus-expressing ß5i (Ad-ß5i) or angiotensin II type 1 receptor (AT1R)-associated protein (Ad-ATRAP), which inhibits AT1R. The ß5i expression and chymotrypsin-like activity were most significantly elevated in Ang II-infused retinas and serum from patients with hypertensive retinopathy. Moreover, Ang II infusion-induced retinopathy was markedly attenuated in ß5i-KO mice but aggravated in Ad-ß5i-injected mice. Accordingly, ß5i KO markedly restored Ang II-induced downregulation of ATRAP and activation of AT1R downstream mediators, which was further enhanced in Ad-ß5i-injected mice. Interestingly, overexpression of ATRAP significantly abrogated Ang II-induced retinopathy in Ad-ß5i-injected mice. This study found that ß5i promoted Ang II-induced retinopathy by promoting ATRAP degradation and activation of AT1R-mediated signals.

A Multi-Sensor Environmental Perception System for an Automatic Electric Shovel Platform.

Electric shovels have been widely used in heavy industrial applications, such as mineral extraction. However, the performance of the electric shovel is often affected by the complicated working environment and the proficiency of the operator, which will affect safety and efficiency. To improve the extraction performance, it is particularly important to study an intelligent electric shovel with autonomous operation technology. An electric shovel experimental platform for intelligent technology research and testing is proposed in this paper. The core of the designed platform is an intelligent environmental sensing/perception system, in which multiple sensors, such as RTK (real-time kinematic), IMU (inertial measurement unit) and LiDAR (light detection and ranging), have been employed. By appreciating the multi-directional loading characteristics of electric shovels, two 2D-LiDARs have been used and their data are synchronized and fused to construct a 3D point cloud. The synchronization is achieved with the assistance of RTK and IMU, which provide pose information of the shovel. In addition, in order to down-sample the LiDAR point clouds to facilitate more efficient data analysis, a new point cloud data processing algorithm including a bilateral-filtering based noise filter and a grid-based data compression method is proposed. The designed platform, together with its sensing system, was tested in different outdoor environment conditions. Compared with the original LiDAR point cloud, the proposed new environment sensing/perception system not only guarantees the characteristic points and effective edges of the measured objects, but also reduces the amount of processing point cloud data and improves system efficiency. By undertaking a large number of experiments, the overall measurement error of the proposed system is within 50 mm, which is well beyond the requirements of electric shovel application. The environment perception system for the automatic electric shovel platform has great research value and engineering significance for the improvement of the service problem of the electric shovel.

Sensitive immunoassay of cardiac troponin I using an optimized microelectrode array in a novel integrated microfluidic electrochemical device.

A sensitive and portable microfluidic electrochemical array device (µFED) was developed for the immunoassay of trace amounts of human cardiac troponin I (cTnI), which is an attractive biomarker for acute myocardial infarction (AMI). The classical "sandwich" method was adopted for the immunoassay. The capture antibody was immobilized using a self-assembled monolayer (SAM) technique, and the process was reorganized to be compatible with the bonding process. The detection antibody was labeled with alkaline phosphatase (AP) for signal amplification. The performance of the µFED was improved by eliminating the shielding effect of the microelectrode array (MEA) integrated in the µFED. The effects of the interstice and the width of the MEA on the response peak current were analyzed and simulated. The concentration gradient, about 3% of the gradient at the surface, was considered as the criterion for estimation of the optimal interstice between electrodes, and its effectiveness was proved. A stable and miniaturized reference electrode was integrated in the µFED, and its potential deviation was less than 5 mV in 15 min. These efforts resulted in the enhanced immunoassay performance of the µFED. A low limit of detection of about 5 pg/mL was obtained in serum samples, and the response current was proportional to the logarithm of concentration from 50 pg/mL to 1 µg/mL. The immunoassay process was accomplished in 15 min. The µFED was thus qualified and is a promising candidate for point-of-care immunoassay of cTnI. Graphical abstract.

Advances on the in vivo and in vitro glycosylations of flavonoids.

Flavonoids possess diverse bioactivity and potential medicinal values. Glycosylation of flavonoids, coupling flavonoid aglycones and glycosyl groups in conjugated form, can change the biological activity of flavonoids, increase water solubility, reduce toxic and side effects, and improve specific targeting. Therefore, it is desirable to synthesize various flavonoid glycosides for further investigation on their medicinal values. Compared with chemical glycosylations, biotransformations catalyzed by uridine diphospho-glycosyltransferases provide an environmentally friendly way to construct glycosidic bonds without repetitive chemical synthetic steps of protection, activation, coupling, and deprotection. In this review, we will summarize the existing knowledge on the biotechnological glycosylation reactions either in vitro or in vivo for the synthesis of flavonoid O- and C-glycosides and other rare analogs.Key points• Flavonoid glycosides usually show improved properties compared with their flavonoid aglycones.• Chemical glycosylation requires repetitive synthetic steps and purifications.• Biotechnological glycosylation reactions either in vitro or in vivo were discussed.• Provides representative synthetic examples in detail.

The association of plasma peroxiredoxin 3 with insulin in pregnant women.

Peroxiredoxin 3 (PRX3) is predominantly located in mitochondria and plays a major role in scavenging hydrogen peroxide of mitochondria. In the present study, we detected plasma PRX3 in pregnant women receiving oral glucose tolerance test at 24-28 gestational weeks. Plasma PRX3 was significantly increased about 1 h later than insulin secretion. In vitro detection of PRX3 in mouse islet cells showed up-regulation by more than 2-fold at 1 h and reached its top at 2 h of glucose stimulation, and the PRX3 level in cultured mediums was concomitantly elevated in a glucose concentration-dependent manner. In addition, both fasting plasma insulin and PRX3 were significantly higher in the subjects of term pregnancy as compared to that at 24-28 gestational weeks, and there was a positive correlation between plasma PRX3 and insulin. Our results indicate that PRX3 plays an active role in the response to insulin release. The positive association of plasma PRX3 and insulin suggest PRX3 to be a potential indicator of high insulin resistance.

Plasma level of peroxiredoxin 3 in patients with polycystic ovarian syndrome.

BACKGROUND: As a member of peroxiredoxin (PRX) family, PRX3 is predominantly located in mitochondria and plays an important role of free radical scavenging. Since a body of evidence demonstrated the involvement of PRX3 in insulin secretion, insulin sensitivity, and glucose metabolism, the present study was conducted to investigate the role of PRX3 in the pathogenesis of polycystic ovarian syndrome (PCOS) featured in insulin resistance. METHODS: Enzyme-linked immunosorbent assay was performed to detect plasma PRX3 in PCOS patients and control subjects. Levels of reactive oxygen species (ROS) and oxidized PRXs were detected in mouse islet cells treated with gradient glucose. RESULTS: We did not find significant difference of fasting plasma PRX3 between PCOS patients and controls. No association was noticed between fasting plasma PRX3 and fasting plasma glucose or insulin. After oral glucose tolerance test (OGTT), PCOS patients showed higher levels of both glucose and insulin as compared to controls. The plasma level of PRX3 was significantly increased at 2 h and began to fall back at 3 h of OGTT. There was a one-hour time lag of peak values between plasma PRX3 and insulin, and the plasma PRX3 at 2 h was positively correlated with the insulin level at 1 h of OGTT of PCOS patients. In addition, the level of ROS was significantly elevated at 1 h and oxidized PRX3 was increased dramatically at 2 h of 16.7mM glucose stimulation in mouse islet cells. CONCLUSION: It seems that PRX3 does not show its antioxidant function under baseline conditions. Instead, PRX3 responds to oxidative stress induced by rapid increase of insulin and glucose in patients with PCOS.

Double-Helical Nanostructures with Controllable Handedness in Bulk Diblock Copolymers.

Double-helical nanostructures with controllable handedness in bulk materials is of high interest in science and technology for the design and fabrication of new materials, in particular metamaterials, which mimic their natural homologues or even show superior properties. Herein, we report the fabrication of double-helical structures with controlled handedness through the self-assembly of an achiral diblock copolymer doped with d- and l-tartaric acid (TA). The helices showed clear handedness dependence on the chirality of the TA. The chiral arrangement of different achiral tectonic units, such as nanoparticles and organic molecules, was confirmed using this helical structure as a template. The double-helical structure will provide new knowledge for understanding the function of helices, and will enable the application of these systems as chiroptical materials.

Sonic hedgehog signaling pathway mediates development of hepatocellular carcinoma.

Although abnormal activation of the sonic hedgehog (Shh) signaling pathway has been demonstrated in human hepatocellular carcinoma (HCC) patients and in most HCC cell lines, the mechanism by which the Shh pathway promotes the development of HCC remains uncertain. Using a liver cancer model induced by diethylnitrosamine (DEN) which mimics the process from liver injury, abnormal hepatocyte proliferation, and hepatocirrhosis to hepatocyte canceration, we investigated the abnormal activation of the Shh pathway by examining the expression of Shh, patched-1 (Ptch), smoothened (SMO), and glioma-associated oncogene-1 (Gli1) genes. During this process, the expression of CDK1 and cyclin B1 protein, which are two components of the M-phase promoting factor (MPF) controlling G2/M transition, was also examined to explore the potential relationship between Shh activation and cell cycle progression. We observed that the cells with Shh, Ptch, and Gli1 protein expression were mainly distributed in hyperplastic nodule, cancerous node, the epithelia of interlobular bile duct, and precancerous tissues. A gradually increasing tendency of the positive expression rate of Shh, Ptch, and Gli1 proteins in the process from the beginning normal tissue to the final cancer formation was revealed. The cyclin B1 and CDK1 expression level was higher in the DEN-induced rats as compared with normal rats, and their expression was mainly distributed in the portal area of the liver, hyperplastic nodule, cancerous node, and precancerous tissues. Our results suggested that the Shh signaling pathway is activated during liver carcinogenesis, and activated Shh signaling promotes the cell proliferation by facilitating the G2/M transition through increasing the expression of cyclin B1 and CDK1 protein, which eventually results in the development of liver cancer. Better understanding of the Shh signaling pathway in HCC may contribute to the development of novel therapeutic strategies in inhibiting cell proliferation and promoting cell cycle arrest.

Effect of yizhitongxuan decoction on learning and memory ability, Gaq/11 expression and Na(+)-K(+)-ATP enzyme activity in rat models of Alzheimer's disease.

OBJECTIVE: To study the effects of Yizhitongxuan decoction on learning and memory abilities, Gaq/11 expression and Na(+)-K(+)-ATP enzyme activity in rat models of Alzheimer's disease (AD) caused by injecting Abeta25-35 into the hippocampus. METHODS: Ninety male Wistar rats (age > or = 10 months) were selected and injected with Abeta25-35 into their hippocampi to establish model animals, which were randomly divided into six groups including a sham-operated group (blank group), a model group, a donepezil HCL group (Western Medicine group), and a high/general/dilute concentrations of Yizhitongxuan decoction groups (TCM I II III group). The Morris water maze was used to examine the learning and memory abilities of rats in each group by place navigation and spatial probe tests. Then, the rats were sacrificed to collect the hippocampi for biochemical tests, using western blotting to detect the expression of Gaq/11 and an ultramicro Na(+)-K(+)-ATP enzyme kit to measure Na(+)-K(+)-ATP enzyme activity. RESULTS: Yizhitongxuan decoction improved model rats' learning and memory abilities, and increased the expression of Gaq/11 in the hippocampus and the level of Na(+)-K(+)-ATP enzyme activity in brain tissue. CONCLUSION: Yizhitongxuan decoction could improve model rats' learning and memory abilities, and had a regulating effect on the expression of Gaq/11 and Na(+)-K(+)-ATP enzyme activity.

Ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS) combined with molecular biomarkers in predicting axillary lymph node metastasis of clinical T1-T2 breast cancer.

Background: In the post-American College of Surgeons Oncology Group Z0011 trial era, clinicians are attempting to preoperatively evaluate axillary lymph node (ALN) status using ultrasound. However, the value of preoperative ultrasound examination remains uncertain. The study aimed to investigate the ultrasonic features of automated breast volume scanner (ABVS) and handheld ultrasound (HHUS), in combination with molecular biomarkers, to predict the risk of ALN metastasis (ALNM) in clinical T1-T2 breast cancer. Methods: A retrospective case-control analysis was conducted on 168 patients with clinical T1-T2 breast cancer at Peking University First Hospital between January 2013 and August 2021. Preoperative ABVS and HHUS examinations were performed. According to the pathology results of the ALN, patients were divided into metastatic and nonmetastatic groups. Logistic regression analyses were used to analyze the ultrasonic characteristics of ABVS and HHUS on clinical T1-T2 breast cancer, and molecular biomarkers were incorporated to predict the risk of ALNM. Results: Of the 168 patients, 88 (52.4%) had ipsilateral ALNM while 80 (47.6%) had no ipsilateral ALNM. The univariate analysis showed that shorter tumor-skin distance (P=0.011), the Adler blood flow grade of II-III (P=0.014), and larger tumor size on ABVS (P<0.001) were associated with ALNM. The multivariate logistic analysis showed that these three risk factors, including the tumor-skin distance [odds ratio (OR) =0.279; P=0.024], the Adler blood flow grade (OR =2.164; P=0.046), and the tumor size on ABVS (OR =1.033; P=0.002), were independent predictive parameters. Conclusions: The tumor-skin distance, tumor size on ABVS, and Adler blood flow grade have diagnostic value for ALNM in clinical T1-T2 breast cancer.