Activation of the NLRP1 Inflammasome and Its Role in Transmissible Gastroenteritis Coronavirus Infection.

The inflammasome pathway is a critical early response mechanism of the host that detects pathogens, initiates the production of inflammatory cytokines, and recruits effector cells to the infection site. Nonetheless, the mechanism of inflammasome activation in coronavirus infection and its biological functions in host defense remain unclear. Transmissible gastroenteritis virus (TGEV), a member of the genus Alphacoronavirus, is a significant pathogen that mainly infects piglets and causes intestinal inflammation and inflammatory cell infiltration. Here, we investigated the mechanism of inflammasome activation in intestinal epithelial cells (IECs) infected with TGEV. We observed a substantial increase in interleukin 1ß (IL-1ß) and IL-18 levels in both IECs and TGEV-infected porcine intestinal tissues. Furthermore, TGEV infection resulted in increased activation of caspase-1 and the NLRP1 (NOD-like receptor [NLR]-containing pyrin domain [PYD]) inflammasome. Our findings revealed that TGEV infection impeded the interaction between porcine NLRP1 (pNLRP1) and porcine dipeptidyl peptidases 9 (pDPP9), yet it did not reduce the expression of pDPP9. Importantly, the ZU5 domain, not the function-to-find domain (FIIND) reported in human NLRP1, was identified as the minimal domain of pNLRP1 for pDPP9 binding. In addition, the robust type I IFN expression induced by TGEV infection also upregulated pNLRP1 expression and pNLRP1 itself acts as an interferon-stimulated gene to counteract TGEV infection. Our data demonstrate that pNLRP1 has antiviral capabilities against coronavirus infection, which highlights its potential as a novel therapeutic target for coronavirus antiviral therapy. IMPORTANCE Coronavirus primarily targets the epithelial cells of the respiratory and gastrointestinal tracts, leading to damage in both humans and animals. NLRP1 is a direct sensor for RNA virus infection which is highly expressed in epithelial barrier tissues. However, until recently, the precise molecular mechanisms underlying its activation in coronavirus infection and subsequent downstream events remained unclear. In this study, we demonstrate that the alphacoronavirus TGEV induces the production of IL-1ß and IL-18 and upregulates the expression of pNLRP1. Furthermore, we found that pNLRP1 can serve as an interferon-stimulated gene (ISG) to inhibit the infection of enterovirus TGEV. Our research highlights the crucial role of NLRP1 as a regulator of innate immunity in TGEV infection and shows that it may serve as a potential therapeutic target for the treatment of coronavirus infection.

Temporal structured illumination and vision-transformer enables large field-of-view binary snapshot ptychography.

Ptychography, a widely used computational imaging method, generates images by processing coherent interference patterns scattered from an object of interest. In order to capture scenes with large field-of-view (FoV) and high spatial resolution simultaneously in a single shot, we propose a temporal-compressive structured-light Ptychography system. A novel three-step reconstruction algorithm composed of multi-frame spectra reconstruction, phase retrieval, and multi-frame image stitching is developed, where we employ the emerging Transformer-based network in the first step. Experimental results demonstrate that our system can expand the FoV by 20× without losing spatial resolution. Our results offer huge potential for enabling lensless imaging of molecules with large FoV as well as high spatial-temporal resolutions. We also notice that due to the loss of low-intensity information caused by the compressed sensing process, our method so far is only applicable to binary targets.

Quantifying uncertainty: Air quality forecasting based on dynamic spatial-temporal denoising diffusion probabilistic model.

Air pollution constitutes a substantial peril to human health, thereby catalyzing the evolution of an array of air quality prediction models. These models span from mechanistic and statistical strategies to machine learning methodologies. The burgeoning field of deep learning has given rise to a plethora of advanced models, which have demonstrated commendable performance. However, previous investigations have overlooked the salience of quantifying prediction uncertainties and potential future interconnections among air monitoring stations. Moreover, prior research typically utilized static predetermined spatial relationships, neglecting dynamic dependencies. To address these limitations, we propose a model named Dynamic Spatial-Temporal Denoising Diffusion Probabilistic Model (DST-DDPM) for air quality prediction. Our model is underpinned by the renowned denoising diffusion model, aiding us in discerning indeterminacy. In order to encapsulate dynamic patterns, we design a dynamic context encoder to generate dynamic adjacency matrices, whilst maintaining static spatial information. Furthermore, we incorporate a spatial-temporal denoising model to concurrently learn both spatial and temporal dependencies. Authenticating our model's performance using a real-world dataset collected in Beijing, the outcomes indicate that our model eclipses other baseline models in terms of both short-term and long-term predictions by 1.36% and 11.62% respectively. Finally, we conduct a case study to exhibit our model's capacity to quantify uncertainties.

Risk factor analysis and establishment of a nomogram model to predict blood loss during total knee arthroplasty.

PURPOSE: The risk factors for excessive blood loss and transfusion during total knee arthroplasty (TKA) remain unclear. The present study aimed to determine the risk factors for excessive blood loss and establish a predictive model for postoperative blood transfusion. METHODS: This retrospective study included 329 patients received TKA, who were randomly assigned to a training set (n = 229) or a test set (n = 100). Univariate and multivariate linear regression analyses were used to determine risk factors for excessive blood loss. Univariate and multivariate logistic regression analyses were used to determine risk factors for blood transfusion. R software was used to establish the prediction model. The accuracy and stability of the models were evaluated using calibration curves, consistency indices, and receiver operating characteristic (ROC) curve analysis. RESULTS: Risk factors for excessive blood loss included timing of using a tourniquet, the use of drainage, preoperative ESR, fibrinogen, HCT, ALB, and free fatty acid levels. Predictors in the nomogram included timing of using a tourniquet, the use of drainage, the use of TXA, preoperative ESR, HCT, and albumin levels. The area under the ROC curve was 0.855 (95% CI, 0.800 to 0.910) for the training set and 0.824 (95% CI, 0.740 to 0.909) for the test set. The consistency index values for the training and test sets were 0.855 and 0.824, respectively. CONCLUSIONS: Risk factors for excessive blood loss during and after TKA were determined, and a satisfactory and reliable nomogram model was designed to predict the risk for postoperative blood transfusion.

Long-Term Expanding Porcine Airway Organoids Provide Insights into the Pathogenesis and Innate Immunity of Porcine Respiratory Coronavirus Infection.

Respiratory coronaviruses cause serious health threats to humans and animals. Porcine respiratory coronavirus (PRCoV), a natural transmissible gastroenteritis virus (TGEV) mutant with partial spike deletion, causes mild respiratory disease and is an interesting animal respiratory coronavirus model for human respiratory coronaviruses. However, the absence of robust ex vivo models of porcine airway epithelium hinders an understanding of the pathogenesis of PRCoV infection. Here, we generated long-term porcine airway organoids (AOs) derived from basal epithelial cells, which recapitulate the in vivo airway complicated epithelial cellularity. Both 3D and 2D AOs are permissive for PRCoV infection. Unlike TGEV, which established successful infection in both AOs and intestinal organoids, PRCoV was strongly amplified only in AOs, not intestinal organoids. Furthermore, PRCoV infection in AOs mounted vigorous early type I and III interferon (IFN) responses and upregulated the expression of overzealous inflammatory genes, including pattern recognition receptors (PRRs) and proinflammatory cytokines. Collectively, these data demonstrate that stem-derived porcine AOs can serve as a promising disease model for PRCoV infection and provide a valuable tool to study porcine respiratory infection. IMPORTANCE Porcine respiratory CoV (PRCoV), a natural mutant of TGEV, shows striking pathogenetic similarities to human respiratory CoV infection and provides an interesting animal model for human respiratory CoVs, including SARS-CoV-2. The lack of an in vitro model recapitulating the complicated cellularity and structure of the porcine respiratory tract is a major roadblock for the study of PRCoV infection. Here, we developed long-term 3D airway organoids (AOs) and further established 2D AO monolayer cultures. The resultant 3D and 2D AOs are permissive for PRCoV infection. Notably, PRCoV mediated pronounced IFN and inflammatory responses in AOs, which recapitulated the inflammatory responses associated with PRCoV in vivo infection. Therefore, porcine AOs can be utilized to characterize the pathogenesis of PRCoV and, more broadly, can serve as a universal platform for porcine respiratory infection.

Different Mechanisms Are Utilized by Coronavirus Transmissible Gastroenteritis Virus To Regulate Interferon Lambda 1 and Interferon Lambda 3 Production.

Type III interferons (IFN-λ) are shown to be preferentially produced by epithelial cells, which provide front-line protection at barrier surfaces. Transmissible gastroenteritis virus (TGEV), belonging to the genus Alphacoronavirus of the family Coronaviridae, can cause severe intestinal injuries in porcine, resulting in enormous economic losses for the swine industry, worldwide. Here, we demonstrated that although IFN-λ1 had a higher basal expression, TGEV infection induced more intense IFN-λ3 production in vitro and in vivo than did IFN-λ1. We explored the underlying mechanism of IFN-λ induction by TGEV and found a distinct regulation mechanism of IFN-λ1 and IFN-λ3. The classical RIG-I-like receptor (RLR) pathway is involved in IFN-λ3 but not IFN-λ1 production. Except for the signaling pathways mediated by RIG-I and MDA5, TGEV nsp1 induces IFN-λ1 and IFN-λ3 by activating NF-κB via the unfolded protein responses (UPR) PERK-eIF2α pathway. Furthermore, functional domain analysis indicated that the induction of IFN-λ by the TGEV nsp1 protein was located at amino acids 85 to 102 and was dependent on the phosphorylation of eIF2α and the nuclear translocation of NF-κB. Moreover, the recombinant TGEV with the altered amino acid motif of nsp1 85-102 was constructed, and the nsp1 (85-102sg) mutant virus significantly reduced the production of IFN-λ, compared with the wild strain. Compared to the antiviral activities of IFN-λ1, the administration of IFN-λ3 showed greater antiviral activity against TGEV infections in IPEC-J2 cells. In summary, our data point to the significant role of IFN-λ in the host innate antiviral responses to coronavirus infections within mucosal organs and in the distinct mechanisms of IFN-λ1 and IFN-λ3 regulation. IMPORTANCE Coronaviruses cause infectious diseases in various mammals and birds and exhibit an epithelial cell tropism in enteric and respiratory tracts. It is critical to explore how coronavirus infections modulate IFN-λ, a key innate cytokine against mucosal viral infection. Our results uncovered the different processes of IFN-λ1 and IFN-λ3 production that are involved in the classical RLR pathway and determined that TGEV nsp1 induces IFN-λ1 and IFN-λ3 production by activating NF-κB via the PERK-eIF2α pathway in UPR. These studies highlight the unique regulation of antiviral defense in the intestine during TGEV infection. We also demonstrated that IFN-λ3 induced greater antiviral activity against TGEV replication than did IFN-λ1 in IPEC-J2 cells, which is helpful in finding a novel strategy for the treatment of coronavirus infections.

Multi-focused electric and magnetic field sourcing from an azimuthally polarized vortex circular hyperbolic umbilic beam.

In this paper, one kind of multi-focusing electric and magnetic field which is sourced from an azimuthally polarized vortex circular hyperbolic umbilic beam (APVCHUB) is presented. After passing through a high NA objective, both the electric and magnetic fields of the APVCHUBs will focus multiple times, and a high-purity longitudinal magnetic field (p q =80%) will be generated. Besides, the mutual induction of the vortex phase and azimuthal polarization changes the electric and magnetic fields' vibration state and intensity distribution, making the longitudinal magnetic field carry an m-order concentric vortex. Our findings suggest that the APVCHUB could have potential applications in magnetic particle manipulation, extremely weak magnetic detection, data storage, semiconductor quantum dot excitation, etc.

Mitochondria-targeted pentacyclic triterpenoid carbon dots for selective cancer cell destruction via inducing autophagy, apoptosis, as well as ferroptosis.

Natural products have been an important database for anti-cancer drug development. However, low water solubility and poor biocompatibility limit the efficacy of natural products. Carbon dots (CDs), as an emerging 0D material, have unique properties in bioimaging, water solubility and biocompatibility. Here, we prepared three pentacyclic triterpenoids (PTs) included glycyrrhetinic acid (GA), ursolic acid (UA) and oleanolic acid (OA), which have anticancer activity but poor water solubility, as raw materials into CDs to improve disadvantages. Our data indicated that the active surface groups of all three CDs were largely preserved and were able to excite green fluorescence. Their carboxyl edges not only exhibited excellent water solubility, but also specifically targeted tumor cell mitochondria due to high sensitivity to ROS-induced damage and high internal oxidative stress. In cancer cells, the PT-CDs induced cell death through three pathways (apoptosis, ferroptosis, and autophagy), which is essentially the same way their raw materials induce death, but the effect was much stronger than raw materials. Notably, functionalized PT-CDs also exhibited extremely low toxicity. In summary, PT-CDs not only have improved water solubility and biocompatibility, but also retain the structure of their raw materials well and exert better efficacy, which provides new ideas for the development of anti-cancer natural product drugs.

Dual targeting of wild-type p53 and gut microbiota by Magnolol represses key metabolic process and kills CRC cells.

Cancer cells consume considerable glucose quantities and majorly employ glycolysis for ATP generation. This metabolic signature (the Warburg effect) allows cancer cells to channel glucose to biosynthesis to support and maintain their dramatic growth along with proliferation. Currently, our understanding of the metabolic and mechanistic implications of the Warburg effect along with its relationship with biosynthesis remains unclear. Herein, we illustrate that the tumor repressor p53 mediate Magnolol (MAG) triggers colon cancer cell apoptosis. And MAG regulates the glycolytic and oxidative phosphorylation steps through transcriptional modulation of its downstream genes TP53-induced glycolysis modulator and biosynthesis of cytochrome c oxidase, attenuating cell proliferation and tumor growth in vivo and in vitro. Meanwhile, we show that MAG cooperates with its own intestinal microflora characteristic metabolites to repress tumors, especially remarkably declined kynurenine (Kyn)/tryptophan (Trp) ratio. Besides, strong relationships of MAG influenced genes, microbiota, as well as metabolites, were explored. Therefore, we established that p53-microbiota-metabolites function as a mechanism, which enable therapy approaches against metabolism-implicated colorectal cancer, in particular MAG as a prospective candidate for treating colorectal cancer.

Prospective randomized controlled trial on the accuracy of prosthesis positioning in total hip arthroplasty assisted by a newly designed whole-process robotic arm.

INTRODUCTION: The purpose of this article is to study whether the newly designed whole-process total hip arthroplasty (THA) robotic arm can improve the accuracy of prosthesis placement in THA. METHOD: In this study, 72 patients undergoing THA were prospectively included and randomly divided into two groups. The experimental group was treated with THA assisted by a newly designed robotic arm. The control group received THA with conventional surgical methods. The imaging data were compared after operation. RESULT: Compared with the conventional operation, the whole-process robotic arm can more accurately place the acetabular prosthesis in the anteversion safe zone of 5 ~ 25°, but in terms of the inclination angle, whether the reference is the safe zone of 30 ~ 50° or 30 ~ 45°, there is no statistical difference between the two groups. The average lower limb length discrepancy (LLLD) in the experimental group was 3.77 ± 8.31 mm longer than contralateral side, while the counterpart in the control group was 8.39 ± 9.11 mm, with significant difference (P = 0.029). The femoral prosthesis was fixed in neutral position in 35 (100%) cases in the experimental group and only 30 (83.3%) in the control group (P = 0.036). There was no significant difference in the recovery of hip offset, femoral anteversion, and canal fill ratio (CFR) between the two groups. CONCLUSION: Robotic arm can improve the accuracy of anteversion of acetabular cup, restore the consistency of the length of lower limbs, and more accurately implant the femoral prosthesis to the neutral position in the coronal position. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2100044124 (date of registration: 2021-3-11).

Targeting adipokines: A new strategy for the treatment of myocardial fibrosis.

Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life and health, causing huge economic losses.Therefore, it is very significant to find an effective treatment for myocardial fibrosis. Adipokines are mainly derived from adipose tissue and have an prominent regulatory effect on glucose and lipid metabolism, inflammation, immune response and cardiovascular function. Adipose tissue is composed of a variety of cell types, including adipocytes, endothelial cells, macrophages and smooth muscle cells. Adipokines mainly include adiponectin, leptin, resistin, visfatin and omentin, which are synthesized and secreted by adipocytes. More and more evidence shows that adipokines can regulate the progress of cardiac fibrosis. This scientific review provides new ideas for targeting adipokines in the treatment of myocardial fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against myocardial fibrosis based on adipokines activity.

p53: A double-edged sword in tumor ferroptosis.

Ferroptosis is a type of lipid peroxidation-induced cell death that can be regulated in various ways, from changing the activity of antioxidant enzymes to the levels of transcription factors. The p53 tumor suppressor gene is the "guardian of the genome" and is involved in controlling cell survival and division under various pressures. In addition to its effects on apoptosis, autophagy, and cell cycle, p53, through the way of transcription dependent or independent two-way, also regulates the biological processes of tumor cell sensitivity to ferroptosis, including the metabolism of amino acids, nicotinamide adenine dinucleotide phosphate, and lipid peroxidation, as well as the biosynthesis of glutathione, phospholipids, NADPH and coenzyme Q10. As reviewed here, we summarized the metabolic network of p53 and its signaling pathway in regulating ferroptosis and elucidated possible factors and potential clinical application of p53 regulating ferroptosis. This review will provide a basis for further understanding the role of p53 in tumor ferroptosis and new strategies for cancer therapeutic avenues.

Maturation and survival of arteriovenous fistula: The challenge starts from the preoperative assessment stage.

BACKGROUND: It is necessary to assess the association between the preoperative indicators and the maturation and survival of arteriovenous fistula (AVF). METHODS: We retrospectively identified 236 patients with a new AVF created between 2016 and 2018 in our Dialysis Center. RESULTS: Multivariate Logistic regression showed that preoperative arterial diameter (odds ratio [OR] = 1.452, 95% confidence interval [CI] [1.233, 1.710], p < 0.001), preoperative venous diameter (OR = 1.296, 95% CI [1.166, 1.477], p < 0.001), left ventricular ejection fraction (LVEF) (OR = 1.187, 95% CI [1.103, 1.277], p < 0.001), and diabetes mellitus (OR = 0.245, 95% CI [0.107, 0.560], p = 0.01) were independent influential factors for AVF maturation. Two years after the AVF surgery follow-up, multivariate Cox proportional-hazards model showed that the preoperative arterial diameter (OR = 0.510, 95% CI [0.320, 0.813], p = 0.005), preoperative venous diameter (OR = 0.940, 95% CI [0.897, 0.985], p = 0.010) and diabetes mellitus (OR = 1.785, 95% CI [1.117, 2.855], p = 0.016) was prognostic factors of AVF survival. The Kaplan-Meier method showed that the primary survival of AVF in patients with different preoperative arterial diameter was statistically significant (log-rank χ2 = 15.415, p < 0.001), while the secondary survival was not statistically significant (log-rank χ2 = 0.131, p = 0.717). CONCLUSION: In our cohort, the preoperative arterial and venous diameter and diabetes mellitus were independent influential factors for AVF maturation and prognostic factors of AVF survival. However, the preoperative LVEF only associated with the maturation of AVF. Meanwhile, smaller arterial diameter (≤2.15 mm) was associated with AVF maturation failure, but did not impact secondary survival of AVF.

The association between the locations of arteriovenous fistulas and patency rates: A systematic review and meta-analysis.

BACKGROUND: The arteriovenous fistulas (AVF) continue to be the most prevalent type of vascular access for hemodialysis (HD). However, the appropriate locations of AVF are controversial. We conducted the meta-analysis to investigate the differences in patency between upper-arm and forearm AVF. METHODS: PubMed, EMBASE, CENTRAL, and ISI Web of Science were searched to identify studies with differences in AVF patency at different locations. Reviewers searched the database, screened studies according to inclusion criteria, and conducted Meta-analysis. RESULTS: A total of 12 studies involving 3437 patients were selected. Pooled data showed that primary patency (PP) of AVF were higher in upper-arm than forearm at 1 and 2 years (odds ratio [OR] = 1.54, p = 0.0005; OR = 2.45, p = 0.001), but the differences in cumulative patency (CP) were not statistically significant at 1 and 2 years (OR = 2.10, p = 0.08; OR = 2.16, p = 0.1). The differences in PP and CP between upper-arm and forearm AVF in patients older than 65 years were not statistically significant at 1 (OR = 1.61, p = 0.05; OR = 2.05, p = 0.17) and 2 years (OR = 3.40, p = 0.13; OR = 1.38, p = 0.16). In Asian patients, the differences in PP and CP between upper-arm and forearm AVF were not statistically significant at 1 (OR = 1.17, p = 0.41; OR = 1.02, p = 0.94) and 2 years (OR = 2.95, p = 0.08; OR = 1.23, p = 0.41). CONCLUSIONS: In this study, the CP of upper-arm and forearm AVF was similar in overall population. There was no difference in PP and CP of AVF between upper-arm and forearm in Asian population or the elderly. The forearm AVF could be consider to be the first choice. for Asian patients or the elderly.

Evaluation of double-high insert mid-term outcomes in cruciate-retaining medial-pivotal total knee arthroplasty - a propensity score-matched analysis with averaged 8-year follow-up.

BACKGROUND: This study aimed to compare the mid-term clinical and radiographic outcomes between medial-pivotal (MP) insert and double-high (DH) insert used under the cruciate-retaining condition in ADVANCE® total knee arthroplasty (TKA). METHODS: The follow-up was conducted for 158 consecutive patients who underwent unilateral ADVANCE® TKA from January 2011 to April 2014. Eighty-four MP inserts and 74 DH inserts were used under cruciate-retaining conditions. A 1:1 propensity score matching (PSM) analysis was performed between MP inserts and DH inserts to compare the clinical and radiographic outcomes. RESULTS: After a 1:1 PSM, 120 patients (60 pairs) were matched between the MP and DH inserts groups. The baseline demographic parameters and clinical scores were comparable between the two groups. The postoperative clinical outcomes at an averaged 8-year follow-up of both groups were significantly improved. The range of motion (ROM) of the DH group was better than that of the MP group, and equivalent Knee Society Function Score (KSFS) between the two groups was found. However, the Knee Society Score (KSS), Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, and Forgotten Joint Score (FJS) of the MP group were found to be significantly superior to those of the DH group. Comparable complication and revision rates were observed between the two groups. The radiographic results were also equally good between MP and DH groups. CONCLUSIONS: Although the mid-term clinical and radiographic outcomes of the DH inserts are fairly good, the clinical scores of the DH group were worse than those of the MP group.

Automatic model for cervical cancer screening based on convolutional neural network: a retrospective, multicohort, multicenter study.

BACKGROUND: The incidence rates of cervical cancer in developing countries have been steeply increasing while the medical resources for prevention, detection, and treatment are still quite limited. Computer-based deep learning methods can achieve high-accuracy fast cancer screening. Such methods can lead to early diagnosis, effective treatment, and hopefully successful prevention of cervical cancer. In this work, we seek to construct a robust deep convolutional neural network (DCNN) model that can assist pathologists in screening cervical cancer. METHODS: ThinPrep cytologic test (TCT) images diagnosed by pathologists from many collaborating hospitals in different regions were collected. The images were divided into a training dataset (13,775 images), validation dataset (2301 images), and test dataset (408,030 images from 290 scanned copies) for training and effect evaluation of a faster region convolutional neural network (Faster R-CNN) system. RESULTS: The sensitivity and specificity of the proposed cervical cancer screening system was 99.4 and 34.8%, respectively, with an area under the curve (AUC) of 0.67. The model could also distinguish between negative and positive cells. The sensitivity values of the atypical squamous cells of undetermined significance (ASCUS), the low-grade squamous intraepithelial lesion (LSIL), and the high-grade squamous intraepithelial lesions (HSIL) were 89.3, 71.5, and 73.9%, respectively. This system could quickly classify the images and generate a test report in about 3 minutes. Hence, the system can reduce the burden on the pathologists and saves them valuable time to analyze more complex cases. CONCLUSIONS: In our study, a CNN-based TCT cervical-cancer screening model was established through a retrospective study of multicenter TCT images. This model shows improved speed and accuracy for cervical cancer screening, and helps overcome the shortage of medical resources required for cervical cancer screening.

Autophagy in vascular dementia and natural products with autophagy regulating activity.

Chronic Cerebral Hypoperfusion(CCH)-induced vascular dementia(VD) is a common neurodegenerative disease which seriously affects the patient's quality of life. Therefore, it is critical to find an effective treatment of VD. Autophagy is a natural regulated mechanism that can remove dysfunctional proteins and organelles, however, over-activation or under-activation can of autophagy can induce the apoptosis of cells. Although autophagy plays a role in the central nervous system is unquestionable, the effects of autophagy in the ischemic brain are still controversial. Some autophagy regulators have been tested, suggesting that both activation and inhibition of autophagy can improve the cognitive function. This article reviews the role of autophagy in CCH-induced VD to discuss whether autophagy has the potential to become a target for drug development and provides several potential compounds for treating vascular dementia.

[Criticalquality attribute assessment of big brand traditional Chinese medicine: visualization method for quality control of Ginkgo Leaves Tablets based on spatial distribution uniformity].

Spatial distribution uniformity is the critical quality attribute(CQA) of Ginkgo Leaves Tablets, a variety of big brand traditional Chinese medicine. The evaluation of the spatial distribution uniformity of active pharmaceutical ingredients(APIs) in Ginkgo Leaves Tablets is important in ensuring their stable and controllable quality. In this study, hyperspectral imaging technology was used to construct the spatial distribution map of API concentration based on three prediction models, further to realize the visualization research on the spatial distribution uniformity of Ginkgo Leaves Tablets. The region of interest(ROI) was selected from each Ginkgo Leaves Tablet, with length and width of 50 pixels, and a total of 2 500 pixels. Each pixel had 288 spectral channels, and the number of content prediction data could reach 1×10~5 for a single sample. The results of the three models showed that the Partial Least Squares(PLS) model had the highest prediction accuracy, with calibration set determination coefficient R_(pre)~2 of 0.987, prediction set determination coefficient R_(pre)~2 of 0.942, root mean square error of calibration(RMSEC) of 0.160%, and root mean square error of prediction(RMSEP) of 0.588%. The classical least-squares(CLS) model had a greater prediction error, with the RMSEP of 0.867%. Multivariate Curve Resolution-Alternating Least Square(MCR-ALS) model showed the worst predictive ability among the three models, and it couldn't realize content prediction. Based on the prediction results of PLS and CLS models, the spatial distribution map of APIs concentration was obtained through three-dimensional data reconstruction. Furthermore, histogram method was used to evaluate the spatial distribution uniformity of API. The data showed that the spatial distribution of APIs in Ginkgo Leaves Tablets was relatively uniform. The study explored the feasibility of visualization of spatial distribution of Ginkgo Leaves Tablets based on three models. The results showed that PLS model had the highest prediction accuracy, and MCR-ALS model had the lowest prediction accuracy. The research results could provide a new strategy for the visualization method of quality control of Ginkgo Leaves Tablets.

[Critical quality attribute assessment of big brand traditional Chinese medicine: process quality control method of Suhuang Zhike Capsules intermediate based on physical properties of powder and granules].

The physical properties of powder and granules are the critical quality attributes for the process control of Suhuang Zhike Capsules, a big brand traditional Chinese medicine. This paper took the production of 25 batches of real-world Suhuang Zhike Capsules dry extract powder and granules intermediates as the research object. Firstly, a method for testing the physical properties of Suhuang Zhike Capsules powder and granules with 19 physical indicators was established. The results showed that the granules of dry extract powder after granulation had a smaller particle size, wider particle size distribution range and poor fluidity, which easily caused the problem of over-limit capsule loading. Secondly, correlation analysis, principal component analysis and cluster analysis were used for mathematical statistics. The correlation analysis showed that the density of dry extract powder could affect the chroma and fluidity. At the same time, the particle size in the granules had a stronger effect on the chroma and fluidity than the density. The study also found that the particle size and hygroscopicity of dry extract powder were potentially key physical properties that affected the physical properties of granules. Furthermore, the results of principal component analysis and cluster analysis showed that the consistency of the physical properties between the dry extract powder and intermediate granules was relatively poor. To this end, similarity analysis was carried out, and the quality control method of powder and granules based on physical fingerprint was established. The results showed that the physical fingerprint similarity of 25 batches of dry extract powder was 0.639-0.976, and the physical fingerprint similarity of the gra-nules was 0.716-0.983. With the similarity of 0.85 as the threshold, the batches with abnormal physical properties could be identified. In this study, the process quality control method of Suhuang Zhike Capsules based on the physical properties of powder and granules was established finally, which realized the identification of abnormal batches, and provided a reference for the process quality control of Suhuang Zhike Capsules.

CTRP13 attenuates vascular calcification by regulating Runx2.

Vascular calcification is strongly associated with increased cardiovascular mortality and morbidity. C1q/TNF-related protein-13 (CTRP13) is a secreted adipokine that plays important roles in the cardiovascular system. However, the functional role of CTRP13 in the development of vascular calcification has yet to be explored. In this study, we collected blood samples from patients with chronic renal failure (CRF) and from rats with adenine-induced CRF. We found that the serum CTRP13 levels were decreased in patients and rats with CRF and were negatively associated with calcium deposition in the abdominal aorta. Compared to those of the controls, ectopic CTRP13 treatment significantly attenuated the calcium accumulation and alkaline phosphatase activity in the abdominal aorta of CRF rats, and ß-glycerophosphate induced the formation of arterial rings and of vascular smooth muscle cells (VSMCs) and decreased the number of VSMCs that transitioned from a contractile to an osteogenic phenotype. The overexpression of Runx2 blocked CTRP13-reduced VSMC calcification. Mechanistically, CTRP13 repressed the phosphorylation of tristetraprolin (TTP), thereby activating TTP and increasing the TTP binding to the 3'untranslated region of the Runx2 mRNA, accelerating the Runx2 mRNA destabilization and degradation. In summary, these findings reveal that CTRP13 regulation is a novel method for the prevention of vascular calcification, representing a novel mechanism of the regulation of Runx2 expression in VSMCs.-Li, Y., Wang, W., Chao, Y., Zhang, F., Wang, C. CTRP13 attenuates vascular calcification by regulating Runx2.