Monocarboxylate transporter 1 in the liver modulates high-fat diet-induced obesity and hepatic steatosis in mice.

BACKGROUND: The monocarboxylate transporter 1 (MCT1) is a member of the MCT family and is implicated in the transport of lactate and a few other monocarboxylates across the cell membrane. How hepatic MCT1 regulates the metabolic functions of the body is currently unknown. METHODS: The functions of hepatic MCT1 on metabolism were analyzed using a mouse model with liver-specific deletion of Slc16a1 that encodes MCT1. Obesity and hepatosteatosis of the mice were induced by high fat diet (HFD). The function of MCT1 on lactate transport was analyzed by measuring lactate level in hepatocytes and mouse liver. Degradation and polyubiquitination of PPARα protein were investigated by biochemical methods. RESULTS: Hepatic deletion of Slc16a1 aggravated high-fat diet (HFD)-induced obesity in female mice, but not in male mice. However, the increased adiposity in Slc16a1-deleted mice was not associated with obvious reductions in metabolic rate and activity. The lactate level of the liver was significantly increased by Slc16a1 deletion in the female mice under HFD condition, suggesting that MCT1 mainly mediated the efflux of lactate in hepatocytes. Deficiency of MCT1 in the liver aggravated HFD-induced hepatic steatosis in both female and male mice. Mechanistically, deletion of Slc16a1 was associated with reduced expressions of genes involved in fatty acid oxidation (FAO) in the liver. The degradation rate and polyubiquitination of PPARα protein were enhanced by Slc16a1 deletion. Blocking the MCT1 function elevated the interaction of PPARα with an E3 ubiquitin ligase HUWE1. CONCLUSIONS: Our findings suggested that the enhanced polyubiquitination and degradation of PPARα upon Slc16a1 deletion likely contributes to the reduced expression of FAO-related genes and aggravation of HFD-induced hepatic steatosis.

CMS-NET: deep learning algorithm to segment and quantify the ciliary muscle in swept-source optical coherence tomography images.

Background: The ciliary muscle plays a role in changing the shape of the crystalline lens to maintain the clear retinal image during near work. Studying the dynamic changes of the ciliary muscle during accommodation is necessary for understanding the mechanism of presbyopia. Optical coherence tomography (OCT) has been frequently used to image the ciliary muscle and its changes during accommodation in vivo. However, the segmentation process is cumbersome and time-consuming due to the large image data sets and the impact of low imaging quality. Objectives: This study aimed to establish a fully automatic method for segmenting and quantifying the ciliary muscle on the basis of optical coherence tomography (OCT) images. Design: A perspective cross-sectional study. Methods: In this study, 3500 signed images were used to develop a deep learning system. A novel deep learning algorithm was created from the widely used U-net and a full-resolution residual network to realize automatic segmentation and quantification of the ciliary muscle. Finally, the algorithm-predicted results and manual annotation were compared. Results: For segmentation performed by the system, the total mean pixel value difference (PVD) was 1.12, and the Dice coefficient, intersection over union (IoU), and sensitivity values were 93.8%, 88.7%, and 93.9%, respectively. The performance of the system was comparable with that of experienced specialists. The system could also successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. Conclusion: We developed an automatic segmentation framework for the ciliary muscle that can be used to analyze the morphological parameters of the ciliary muscle and its dynamic changes during accommodation.

Noninvasive fluid bubble detection based on capacitive micromachined ultrasonic transducers.

Ultrasonic fluid bubble detection is important in industrial controls, aerospace systems and clinical medicine because it can prevent fatal mechanical failures and threats to life. However, current ultrasonic technologies for bubble detection are based on conventional bulk PZT-based transducers, which suffer from large size, high power consumption and poor integration with ICs and thus are unable to implement real-time and long-term monitoring in tight physical spaces, such as in extracorporeal membrane oxygenation (ECMO) systems and dialysis machines or hydraulic systems in aircraft. This work highlights the prospect of capacitive micromachined ultrasonic transducers (CMUTs) in the aforementioned application situations based on the mechanism of received voltage variation caused by bubble-induced acoustic energy attenuation. The corresponding theories are established and well validated using finite element simulations. The fluid bubbles inside a pipe with a diameter as small as 8 mm are successfully measured using our fabricated CMUT chips with a resonant frequency of 1.1 MHz. The received voltage variation increases significantly with increasing bubble radii in the range of 0.5-2.5 mm. Further studies show that other factors, such as bubble positions, flow velocities, fluid medium types, pipe thicknesses and diameters, have negligible effects on fluid bubble measurement, demonstrating the feasibility and robustness of the CMUT-based ultrasonic bubble detection technique.

Hybrid weakness and continuous flowering caused by compound expression of FTLs in Chrysanthemum morifolium × Leucanthemum paludosum intergeneric hybridization.

Hybridization is an important evolutionary mechanism ubiquitous to plants. Previous studies have shown that hybrid polyploidization of cultivated chrysanthemum, 'Zhongshanzigui', and Leucanthemum paludosum exhibit spring-flowering traits. This study explores the function of the LpFTLs gene via the phenotype of A. thaliana after heterologous transformation of the LpFTLs gene, and analyzes the mechanism ofthe continuous flowering phenotype and heterosis of hybrid offspring. The results suggest that the flowering phenotype of hybrid offspring in spring may be related to the expression of the LpFTLs gene. Ectopic expression of Leucanthemum paludosumLpFTLs in Arabidopsis thaliana resulted in earlier flowering, indicating that the LpFTLs gene also affects the flowering time in L. paludosum. Compound expression of FTLs in C. morifolium × L. paludosum intergeneric hybridization directly leads to serious heterosis in the hybrid offspring. Moreover, continuous flowering appears to be accompanied by hybrid weakness under the balance of vegetative and reproductive growth. Therefore, in future studies on chrysanthemum breeding, a suitable balance point must be established to ensure the target flowering time under normal growth.

Relapsed/refractory diffuse large B cell lymphoma with cardiac involvement: A case report and literature review.

Background: Hematological malignancies of the heart (CHMs) are extremely rare, and include leukemia, lymphoma infiltration, and multiple myeloma with extramedullary manifestations. Cardiac lymphoma can be divided into primary cardiac lymphoma (PCL) and secondary cardiac lymphoma (SCL). Compared to PCL, SCL is relatively more common. Histologically, the most frequent SCL is diffuse large B-cell lymphoma (DLBCL). The prognosis of lymphoma in patients with cardiac involvement is extremely poor. CAR T-cell immunotherapy has been recently become a highly effective treatment for relapsed or refractory diffuse large B-cell lymphoma. To date, there are no guidelines that provide a clear consensus on the management of patients with secondary heart or pericardial involvement. We report a case of relapsed/refractory DLBCL that secondarily affected the heart. Case presentation: A male patient was diagnosed with double-expressor DLBCL based on biopsies of mediastinal and peripancreatic masses and fluorescence in situ hybridization. The patient received first-line chemotherapy and anti-CD19 CAR T cell immunotherapy, but developed heart metastases after 12 months. Considering his physical condition and economic situation of the patient, two cycles of multiline chemotherapies were administered, followed by CAR-NK cell immunotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) at another hospital. After achieving a six-month survival, the patient died of severe pneumonia. Conclusion: The response of our patient emphasizes the importance of early diagnosis and timely treatment to improve the prognosis of SCL and serves as an important reference for SCL treatment strategies.

Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1ß, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.

The application of nanopore targeted sequencing in the diagnosis and antimicrobial treatment guidance of bloodstream infection of febrile neutropenia patients with hematologic disease.

Traditional microbiological methodology has limited sensitivity, detection range, and turnaround times in diagnosis of bloodstream infection in Febrile Neutropenia (FN) patients. A more rapid and sensitive detection technology is urgently needed. Here we used the newly developed Nanapore targeted sequencing (NTS) to diagnose the pathogens in blood samples. The diagnostic performance (sensitivity, specificity and turnaround time) of NTS detection of 202 blood samples from FN patients with hematologic disease was evaluated in comparison to blood culture and nested Polymerase Chain Reaction (PCR) followed by sanger sequence. The impact of NTS results on antibiotic treatment modification, the effectivity and mortality of the patients under the guidance of NTS results were assessed. The data showed that NTS had clinical sensitivity of 92.11%, clinical specificity of 78.41% compared with the blood culture and PCR combination. Importantly, the turnaround time for NTS was <24 h for all specimens, and the pre-report time within 6 h in emergency cases was possible in clinical practice. Among 118 NTS positive patients, 98.3% patients' antibiotic regimens were guided according to NTS results. There was no significant difference in effectivity and mortality rate between Antibiotic regimen switched according to NTS group and Antibiotic regimen covering pathogens detected by NTS group. Therefore, NTS could yield a higher sensitivity, specificity and shorter turnaround time for broad-spectrum pathogens identification in blood samples detection compared with traditional tests. It's also a good guidance in clinical targeted antibiotic treatment for FN patients with hematologic disease, thereby emerging as a promising technology for detecting infectious disease.

Myeloid leukemia factor 1: A "double-edged sword" in health and disease.

The occurrence and development of malignancies are closely related to abnormal cell cycle regulation. Myeloid leukemia factor 1 (MLF1) is a small nucleocytoplasmic shuttling protein associated with cell cycle exit, apoptosis, and certain immune functions. Therefore, it is pertinent to explore the role of MLF1 in health and diseases. Studies to date have suggested that MLF1 could act as a double-edged sword, regulating biochemical activities directly or indirectly. In hematopoietic cells, it serves as a protective factor for the development of lineages, and in malignancies, it serves as an oncogenesis factor. The diversity of its functions depends on the binding partners, including tumor inhibitors, scaffolding molecules, mitochondrial membrane proteins, and transcription factors. Emerging evidence indicates that MLF1 influences immune responses as well. This paper reviews the structure, biological function, and research progress on MLF1 in health and diseases to provide new insights for future research.

Drug resistance analysis of three types of avian-origin carbapenem-resistant Enterobacteriaceae in Shandong Province, China.

Animal-derived Enterobacteriaceae bacteria such as Escherichia coli (E. coli), Proteus mirabilis (P. mirabilis), and Klebsiella pneumoniae (K. pneumoniae) are important food-borne zoonotic bacilli that exist widely in the broiler-breeding industry. Although carbapenem antibiotics are considered to be the last line of defense against multidrug-resistant bacteria, carbapenem-resistant Enterobacteriaceae (CRE) break through them. In our study, we therefore, examined the prevalence of CRE and characteristics of antimicrobial resistance in 6 conventional broiler-fattening farms in Shandong Province, China. Our study revealed isolation rates of 3.57% (6/168) for carbapenem-resistant E. coli, 10% (5/50) for carbapenem-resistant P. mirabilis, and 3.03% (1/33) for carbapenem-resistant K. pneumoniae. All 12 CRE bacterial strains showed varying degrees of resistance to 27 antibiotics in 8 classes and were multidrug-resistant. The rate of the strains containing blaNDM genes, at 91.67% (11/12), was especially high. Among other results, the carrying rate of integrons in CRE bacteria was 91.67% (11/12), and 2 strains carried both class I and class II integrons, which accelerated the lateral transmission of resistant bacteria. Our first-ever finding of the 3 CRE bacteria E. coli, P. mirabilis, and K. pneumoniae on the same broiler farm suggests that poultry-derived CRE strains may pose a risk to humans. Moreover, our findings from surveillance can inform current understandings of the prevalence and characteristics of multidrug-resistant CRE in Shandong Province and, in turn, help to curb threats to food safety and public health and better prevent and control infectious zoonotic diseases.

Ecological risk under the dual threat of heavy metals and antibiotic resistant Escherichia coli in swine-farming wastewater in Shandong Province, China.

Mineral elements and antibiotic-resistant bacterial pollutants in livestock and poultry farms' wastewater are often sources of ecological and public health problems. To understand the heavy-metal pollution status and the characteristics of drug-resistant Escherichia coli (E. coli) in swine-farm wastewater in Shandong Province and to provide guidance for the rational use of mineral-element additives, common antibiotics, and quaternary ammonium compound disinfectants on swine farms, 10 mineral elements were measured and E. coli isolated from wastewater and its resistance to 29 commonly used antibiotics and resistance genes was determined. Finally, phylogenetic and multi-locus sequence typing (MLST) analyses was performed on E. coli. The results showed serious pollution from iron and zinc, with a comprehensive pollution index of 708.94 and 3.13, respectively. It is worth noting that average iron levels in 75% (12/16) of the districts exceed allowable limits. Multidrug-resistant E. coli were found in every city of the province. The E. coli isolated from swine-farm wastewater were mainly resistant to tetracyclines (95.3%), chloramphenicol (77.8%), and sulfonamides (62.2%), while antibiotic resistance genes for quinolones, tetracyclines, sulfonamides, aminoglycosides, and ß-lactams were all more than 60%. The clonal complex 10 (CC10) was prevalent, and ST10 and ST48 were dominant in E. coli isolates. Multidrug-resistant E. coli were widely distributed, with mainly A genotypes. However, the mechanism of the effect of iron on antibiotic resistance needs more study in this area. Thus, further strengthening the prevention and control of iron and zinc pollution and standardizing the use of antibiotics and mineral element additives in the swine industry are necessary.

Advances in the mechanisms of polysaccharides in alleviating depression and its complications.

BACKGROUND: Depression is one of the most serious mental illnesses worldwide that endangers the health of people. The pathogenesis of depression is complex and is associated with abnormal neurotransmitter levels, activation of the hypothalamic-pituitary-adrenal (HPA) axis, inflammation, and gut flora-related disorders. However, most of the current pharmacological therapies used to manage depression are inconsistent and are associated with side effects. Owing to their low toxicity and wide availability in nature, polysaccharides are gradually attracting attention and are being discovered to exert direct or indirect antidepressant effects. PURPOSE: In this review, we have summarized the classification, dosage, and experimental models to study polysaccharides with antidepressant effects obtained from different sources. We have also reviewed the protective effects and underlying mechanisms of these polysaccharides in depression by modulating inflammation, the HPA axis, and intestinal flora. METHODS: We searched the PubMed, Web of Science, and Google scholar databases and included studies that reported the use of polysaccharides in treating depression. RESULTS: The unique benefits of natural polysaccharides as antidepressants lie in their potential to modulate inflammation, regulate the HPA axis, and regulate intestinal flora, giving full play to their antidepressant effects via multiple pathways and targets. CONCLUSION: Natural polysaccharides may be a promising resource for use as adjuvant antidepressant therapy. Our study might therefore provide evidence for the development of polysaccharide resources as antidepressants.

A Visualized Mortality Prediction Score Model in Hematological Malignancies Patients with Carbapenem-Resistant Organisms Bloodstream Infection.

Background: Bloodstream infection (BSI) due to carbapenem-resistant organisms (CROs) has emerged as a worldwide problem associated with high mortality. This study aimed to evaluate the risk factors associated with mortality in HM patients with CROs BSI and to establish a scoring model for early mortality prediction. Methods: We conducted a retrospective cohort study at our hematological department from January 2018 to December 2021, including all HM patients with CROs BSI. The outcome measured was death within 30-day of BSI onset. Survivor and non-survivor subgroups were compared to identify predictors of mortality. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors and develop a nomogram. Results: In total, 150 HM patients were included in the study showing an overall 30-day mortality rate of 56%. Klebsiella pneumonia was the dominant episode. Cox regression analysis showed that pre-infection length of stay was >14 days (score 41), Pitt score >4 (score 100), mucositis (score 41), CAR (The ratio of C-reactive protein to albumin) >8.8 (score 57), early definitive therapy (score 44), and long-duration (score 78) were positive independent risk predictors associated with 30-day mortality, all of which were selected into the nomogram. Furthermore, all patients were divided into the high-risk group (≥160 points) or the low-risk group based on the prediction score model. The mortality of the high-risk group was 8 times more than the low-risk group. Kaplan-Meier analysis showed that empirical polymyxin B therapy was associated with a lower 30-day mortality rate, which was identified as a good prognostic factor in the high-risk group. In comparison, empirical carbapenems and tigecycline were poor prognostic factors in a low-risk group. Conclusion: Our score model can accurately predict 30-day mortality in HM patients with CROs BSI. Early administration of CROs-targeted therapy in the high-risk group is strongly recommended to decrease mortality.

Screening of a high-yield strain of avermectin B1a by colony analysis in situ / Selección in situ de una cepa de alto rendimiento de avermectina B1a mediante análisis de colonias

Avermectin, an agricultural antibiotic, is widely used as an agricultural insecticide and an important lead compound of antibiotics. It is manufactured by Streptomyces avermitilis through fermentation. Manufacturers pay special attention to screening for strains with high fermentation capacity based on morphological properties of the colony and by the result of shake flask fermentation. These traditional screening methods are time-consuming and labor-intensive and require specialized equipment. Moreover, evaluation of colony appearance is highly subjective. To improve and accelerate the screening process, we developed a rapid in situ screening method. Forty-four strains isolated naturally from the spores of industrial high-yielding strains were studied. The data show that the colony fermentation titer is highly correlated with the yield from the shake flask fermentation of avermectin, and the Pearson’s R is 0.990. The total titer of avermectins by shake flask fermentation is also highly correlated with the B1a titer (Pearson’s R is 0.994). This result also shows that strains can be quickly screened by analyzing the colony titer. Pigment rings of the colonies that appeared after growing and maturing on the new medium plate were analyzed. The chosen colonies were directly marked and punched and then extracted with methanol. The fermentation ability can be evaluated by measuring the absorbance at 245 nm. This methodology can be applied in both natural breeding and mutation breeding conditions. By continuously breeding from 2008 to 2020, the flask titer of avermectin B1a increased from 4582 ± 483 to 9197 ± 1134 μg/mL.(AU)

Early prevention of radial artery occlusion via distal transradial access for primary percutaneous coronary intervention.

Background: Conventional transradial access (TRA) has been the preferred access for coronary intervention. Recently, distal radial access (DRA) is introduced as an alternative choice to reduce radial artery occlusion (RAO) risk. The study sought to assess the impact of DRA on early RAO using Doppler ultrasound in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). Methods: This is a prospective, single-center, open-label randomized clinical trial in which patients with indications for primary PCI from January 2022 to September 2022 were assigned to DRA or TRA group with 100 cases in each group. The primary endpoint was the incidence of forearm RAO, evaluated by Doppler ultrasound before discharge. Results: The rate of access success was comparable between the DRA and TRA groups (98.0 vs. 94.0%, P = 0.279). Compared with the TRA group, longer puncture time was observed in the DRA group [2.4 (1.7-4.2) min vs. 1.7 (1.4-2.3) min; P < 0.001] whereas the door-to-wire time was not delayed in primary PCI [71 (54-88) min vs. 64 (56-82) min, P = 0.103]. Shorter hemostasis time was required in the DRA group [3.1 (2.7-3.3) h vs. 6.2 (5.9-6.4) h; P < 0.001]. Significant reduction of the incidence of forearm RAO was observed in the DRA group (2.0 vs. 9.0%, P = 0.030). Local hematomas ≤ 5 cm was similar in both groups (4.0 vs. 6.0%, P = 0.516), while those > 5 cm were significantly more frequent in the TRA group (0 vs. 6.0%, P = 0.029). Conclusion: Distal radial access is associated with a comparable lower incidence of forearm RAO, shorter hemostasis time, and lower rate of vascular complications compared to TRA in primary PCI. Systematic review registration: [https://www.chictr.org.cn], identifier [ChiCTR2200061841].

Defect-Induced Ultrafast Nonadiabatic Electron-Hole Recombination Process in PtSe2 Monolayer.

Defects are inevitable in two-dimensional materials due to the growth condition, which results in many unexpected changes in materials' properties. Here, we have mainly discussed the nonradiative recombination dynamics of PtSe2 monolayer without/with native point defects. Based on first-principles calculations, a shallow p-type defect state is introduced by a Se antisite, and three n-type defect states with a double-degenerate shallow defect state and a deep defect state are introduced by a Se vacancy. Significantly, these defect states couple strongly to the pristine valence band maximum and lead to the enhancement of the in-plane vibrational Eg mode. Both factors appreciably increase the nonadiabatic coupling, accelerating the electron-hole recombination process. An explanation of PtSe2-based photodetectors with the slow response, compared to conventional devices, is provided by studying this nonradiative transitions process.

Characterization of avain metapneumovirus subgroup C isolated from chickens in Beijing, China.

Avian metapneumovirus (aMPV) is an important causative agent that causes acute respiratory disease and egg-dropping in chickens and turkeys. Here, we characterized an aMPV subgroup C (aMPV/C) from 320-day-old broiler breeder chickens with severe respiratory diseases in Beijing, China, as evidenced by RT-PCR typing and confirmation of the nucleoprotein (N) gene sequence. The N gene sequence of the aMPV/C strain (designated BJ17) exhibited no deletions or insertions and possessed 94.6% to 99.6% identity to those of published aMPV/C isolates. The phylogenetic tree of the nucleotide sequences constructed using the neighbor-joining clustering method showed that the BJ17 strain formed one cluster with other aMPV/C viruses and formed one subcluster with published Chinese aMPV/C isolates regardless of Muscovy duck or chicken origins. Comparative analysis of the N proteins showed that a unique amino acid residue D at position 110 might be associated with regional distribution due to its occurrence in all the Chinese aMPV/C isolates only. Strain BJ17 was successfully isolated by cultured Vero cell passage and further inoculated in 3-wk-old specific-pathogen-free chickens for the examination of pathogenicity. Animal experimental results showed that BJ17-inoculated chickens had severe respiratory diseases and inflammatory lesions, as demonstrated by pathological changes and aMPV antigen in the nasal turbinate, tracheae, and lung tissues. These results enrich the available information regarding the epidemiology and pathogenicity of aMPV/C in chickens, which may facilitate the development of effective measures against aMPV/C infection in China.

A Convolutional Dynamic-Jerk-Planning Algorithm for Impedance Control of Variable-Stiffness Cable-Driven Manipulators.

Cable-driven manipulators, characterized by slender arms, dexterous motion, and controllable stiffness, have great prospects for application to capture on-orbit satellites. However, it is difficult to achieve effective motion planning and stiffness control of cable-driven manipulators because of the coupled relationships between cable lengths, joint angles, and reaction forces. Therefore, a convolutional dynamic-jerk-planning algorithm is devised for impedance control of variable-stiffness cable-driven manipulators. First, a variable-stiffness cable-driven manipulator with universal modules and rotary quick-change modules is designed to overcome difficulties related to disassembly, installation, and maintenance. Second, a convolutional dynamic-jerk-planning algorithm is devised to overcome the discontinuity and shock problems of the manipulator's velocity during intermittent control processes. The algorithm can also make acceleration smooth by setting jerk dynamically, reducing acceleration shock and ensuring the stable movement of the cable-driven manipulator. Third, the stiffness of the cable-driven manipulator is further optimized by compensating for the position and velocity of drive cables by employing position-based impedance control. Finally, the prototype of the variable-stiffness cable-driven manipulator is developed and tested. The convolutional dynamic-jerk-planning algorithm is used to plan the desired velocity curves for velocity control experiments of the cable-driven manipulator. The results verify that the algorithm can improve the acceleration smoothness, thereby making movement smooth and reducing vibrations. Furthermore, stiffness control experiments verify that the cable-driven manipulator has ideal variable stiffness capabilities.

Culprit vessel revascularization first with primary use of a dedicated transradial guiding catheter to reduce door to balloon time in primary percutaneous coronary intervention.

Background: The effect of a single transradial guiding catheter (STGC) for culprit vessel percutaneous coronary intervention (PCI) first on door-to-balloon (D2B) time remains unclear. Materials and methods: Between February 2017 and July 2019, 560 patients with ST-elevation myocardial infarction (STEMI) were randomized into either the STGC group (n = 280) or the control group (n = 280) according to direct culprit vessel PCI with a STGC. In the STGC group, a dedicated transraidal guiding catheter (6F either MAC3.5 or JL3.5) was used for the treatment of electrocardiogram (ECG)-guided culprit vessel first and later contralateral angiography. In the control group, a universal diagnostic catheter (5F Tiger II) was used for complete coronary angiography, followed by guiding catheter selection for culprit vessel PCI. The primary endpoint was D2B time, and the secondary endpoint included catheterization laboratory door-to-balloon (C2B), procedural, fluoroscopy times, and major adverse cardiac events (MACE) at 30 days. Results: The median D2B time was significantly shorter in the STGC group compared to the control group (53.9 vs. 58.4 min; p = 0.003). The C2B, procedural, and fluoroscopy times were also shorter in the STGC group (C2B: 17.3 vs. 24.5 min, p < 0.001; procedural: 45.2 vs. 49.0 min, p = 0.012; and fluoroscopy: 9.7 vs. 11.3 min, p = 0.025). More patients achieved the goal of D2B time within 90 min (93.9% vs. 87.1%, p = 0.006) and 60 min (61.4% vs. 51.1%, p = 0.013) in the STGC group. Radial artery perforation (RAP) was significantly reduced in the STGC group compared with the control group (0.7% vs. 3.2%, P = 0.033). MACE at 30 days was similar (2.5% vs. 4.6%, P = 0.172) between the two groups. Conclusion: ECG-guided immediate intervention on culprit vessel with a STGC can reduce D2B, C2B, procedural, and fluoroscopy times (ECG-guided Immediate Primary PCI for Culprit Vessel to Reduce Door to Device Time; NCT03272451).

P2X7 Receptor in Alcoholic Steatohepatitis and Alcoholic Liver Fibrosis.

Alcoholic liver disease is one of the most common chronic liver diseases in the world. It is a liver disease caused by prolonged heavy drinking and its main clinical features are nausea, vomiting, enlargement of the liver, and jaundice. Recent studies suggest that Kupffer cell-mediated inflammatory response is a core driver in the development of alcoholic steatohepatitis and alcoholic liver fibrosis. As a danger signal, extracellular ATP activates the assembly of NLPR3 inflammasome by acting on purine P2X7 receptor, the activated NLRP3 inflammasome prompts ASC to cleave pro-cCaspase-1 into active caspase-1in KCs. Active caspase-1 promotes the conversion of pro-IL-1ß to IL-1ß, which further enhances the inflammatory response. Here, we briefly review the role of the P2X7R-NLRP3 inflammasome axis in the pathogenesis of alcoholic liver disease and the evolution of alcoholic steatohepatitis and alcoholic liver fibrosis. Regulation of the inflammasome axis of P2X7R-NLRP3 may be a new approach for the treatment of alcoholic liver disease.

NOVA1 promotes NSCLC proliferation and invasion by activating Wnt/ß-catenin signaling.

BACKGROUND: Neuro-oncological ventral antigen 1 (NOVA1) is a neuron-specific RNA-binding protein which regulates alternative splicing in the developing nervous system. Recent research has found that NOVA1 plays a significant role in carcinogenesis. In this paper, we examine the role of NOVA1 in non-small cell lung cancer (NSCLC) and its underlying molecular mechanisms. METHODS: The expression of NOVA1 in NSCLC was detected by immunohistochemistry and correlations between NOVA1 expression and clinicopathological factors were analyzed by chi-square tests. Kaplan-Meier survival analysis and the Cox regression model were used to evaluate the predictive effect of prognostic factors. Western blotting, Cell Counting Kit-8, colony formation, apoptosis, migration and invasion assays were used to detect the effects of silencing (si)NOVA1 RNA on Wnt/ß-catenin signaling and biological behavior in NSCLC cell lines. RESULTS: Our study showed that expression of NOVA1 was up-regulated and significantly correlated with poor differentiation (p = 0.020), advanced TNM stage (P = 0.001), T stage (P = 0.001) and lymph node metastasis (P = 0.000) as well as the expression of ß-catenin (P = 0.012) in NSCLC. The down-regulation of NSCLC by siRNA significantly inhibited proliferation, migration and invasion and promoted apoptosis in NSCLC cells. Expression of Wnt signaling molecules, including ß-catenin, activated ß-catenin, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-7, was also significantly reduced by siNOVA1. The inhibition of Wnt/ß-catenin signaling in A549 and H1299 cells by siNOVA1 was reversed after treatment with a ß-catenin expression plasmid. CONCLUSION: The present study suggests that NOVA1 may serve as a potential prognosis biomarker in NSCLC. High NOVA1 expression was associated with poor survival rate. Finally, in vitro experiments verified that NOVA1 promotes NSCLC cell proliferation and invasion by regulating Wnt/ß-catenin signaling.