A Pan-Cancer Analysis of the Immunological and Prognostic Role of BUB1 Mitotic Checkpoint Serine/Threonine Kinase B (BUB1B) in Human Tumors.

BACKGROUND: BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is a member of the spindle assembly checkpoint family and is related to cancer disease progression, invasion, metastasis, and functional promotion of angiogenesis. Several studies have noted that the BUB1B gene is frequently upregulated in various types of cancers. However, the expression patterns of BUB1B across different cancer types and its diagnostic and prognostic potential have not been investigated from a pan-cancer perspective. METHODS: The Cancer Genome Atlas (TCGA) data were used to explore the diagnostic and prognostic immunological potential of BUB1B in 33 cancer types. RESULTS: BUB1B was almost universally upregulated across all cancers, with increased protein expression in at least six cancer types and an enhanced phosphorylation level of S670 in two cancer types. Furthermore, BUB1B expression was negatively associated with clinical progression and prognosis in most cancers. BUB1B expression was positively associated with tumor mutational burden and microsatellite instability in 17 and 7 cancer types, respectively, and there was a correlation between BUB1B expression and DNA methylation at multiple probes in 30 cancer types. Additionally, a positive relationship existed between BUB1B expression and the infiltration levels of Th2, Tcm, and T helper cells, whereas BUB1B showed a negative correlation with the infiltration levels of other immune cells in multiple cancers. Moreover, functions associated with cell cycle progression and ubiquitin-mediated proteolysis were involved in the functional mechanism of BUB1B. CONCLUSIONS: Our pan-cancer study offers a comprehensive understanding of the role of BUB1B in tumorigenesis and tumor immunity across different types of cancer.

A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism.

The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins. Using a SARS-CoV-2 pseudovirus system, we further identify several drug candidates including Fostamatinib, Linagliptin, Lysergol and Sophoridine that can effectively block the cell entry of SARS-CoV-2 variants into human lung cells even at a nanomolar scale. These efforts not only illuminate the feasibility of applying deep learning-based drug repositioning for antiviral agents by targeting a specified mechanism, but also provide a valuable resource of promising drug candidates or lead compounds to treat COVID-19.

Left atrial appendage closure in nonvalvular atrial fibrillation patients with percutaneous coronary intervention.

OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) concomitant with coronary artery disease (CAD) may increase the risk of thromboembolism. Antithrombotic therapy for NVAF patients with percutaneous coronary intervention (PCI) remains contradictory and challenging. This study aimed to assess the safety and efficacy of left atrial appendage closure (LAAC) in a cohort of patients with NVAF and PCI. METHODS: A total of 109 patients undergoing LAAC procedures between March 2017 and December 2020 were categorized into 2 groups, Group I included 36 patients with PCI while group II included 73 patients without. Peri-procedural and long-term complications, as well as ischemia and bleeding events, were retrospectively analyzed. RESULTS: Group I had more diabetes mellitus (55.6% vs. 26.0%; p = 0.003), higher CHA2DS2-VASc scores (5.44 ± 1.85 vs. 4.22 ± 1.64; p = 0.002) and HAS-BLED scores (3.39 ± 0.93 vs. 2.74 ± 1.05; p = 0.003) compared to Group II. Procedure-related complications within 7 days were similar in both groups (8.3% vs. 8.2%; P = 1.000). Over a median follow-up period of 20.9 months, there were no significant differences between two subgroups with regard to cardiovascular death (2.8% vs. 0%, p = 0.330), stroke/transient ischemic attack (2.8% vs. 5.5%, p = 1.000), major bleeding (0% vs. 2.7%, p = 1.000) and device-related thrombus (8.3% vs. 1.4%, p = 0.104). The observed annualized thromboembolic and major bleeding events determined by Kaplan-Meier analysis decreased by 82.4% and 100% in group I, 55.9% and 75.8% in group II, respectively. CONCLUSION: LAAC is a safe and effective option for stroke prevention in NVAF patients with PCI.

LncRNA UCA1, miR-26a, and miR-195 in coronary heart disease patients: Correlation with stenosis degree, cholesterol levels, inflammatory cytokines, and cell adhesion molecules.

BACKGROUND: Long noncoding RNA urothelial cancer-associated 1 (lnc-UCA1) targets microRNA-26a (miR-26a) and microRNA-195 (miR-195) to participate in coronary heart disease (CHD) progression via regulation of vascular smooth muscle cell and microvascular endothelial cell viability and mobility. Therefore, this study set out to further explore the relationship between lnc-UCA1 and miR-26a and miR-195, along with their roles in the management of patients with CHD. METHODS: One hundred and thirty-six CHD patients and 70 age-/gender-matched controls were recruited in this case-control study. Their peripheral blood mononuclear cell samples were collected for lnc-UCA1, miR-26a, and miR-195 measurement. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecules measurement. The Gensini score was used to evaluate the stenosis severity in CHD patients. RESULTS: Lnc-UCA1 expression tend to be increased, while miR-26a and miR-195 expressions were reduced in patients with CHD compared to that of controls (all p < 0.001). In CHD patients, lnc-UCA1 was negatively correlated with miR-26a (p < 0.001) and miR-195 (p = 0.014). Besides, lnc-UCA1 was positively correlated with Gensini score (p < 0.001), total cholesterol (p = 0.019), low-density lipoprotein cholesterol (p = 0.002), and C-reactive protein (p < 0.001), while miR-26a (p < 0.001) and miR-195 (p = 0.002) were negatively correlated with Gensini score. What's more, lnc-UCA1 was positively correlated with tumor necrosis factor (TNF)-α (p = 0.004), interleukin (IL)-1ß (p = 0.041), vascular cell adhesion molecule-1 (VCAM-1) (p = 0.010), and intercellular adhesion molecule-1 (ICAM-1) (p < 0.001). While miR-26a was negatively correlated with some of the individual inflammatory cytokines and cell adhesion molecules. CONCLUSION: Lnc-UCA1, miR-26a, and miR-195 may serve as potential biomarkers for CHD management.

Decomposition and decoupling analysis of carbon emissions from agricultural economic growth in China's Yangtze River economic belt.

In this study, carbon emissions from agricultural energy consumption (CEAEC) are fully analyzed using data from the Yangtze River Economic Belt (YEB) between 2000 and 2017. First, generalized LMDI is adopted to decompose the drivers of CEAEC into five components. Then, the decoupling indicator and the decoupling effort indicator are constructed to quantify the decoupling degrees and examine the government's emission reduction efforts, respectively. The results show that (1) CEAEC in the YEB has shown a phased increase, reaching a peak at 1732.25104t in 2012. Except for some decreases found in Shanghai, Chongqing, and Guizhou, it is shown that all provinces' CEAEC have risen to varying degrees. In contrast, the intensity of CEAEC in the YEB has been declining since 2005. (2) The economic output effect acts as the major contributor to the growth of CEAEC, followed by the population effect. In contrast, both the energy intensity effect and the energy structure effect are the primary reasons for reductions in CEAEC. The spatial difference in CEAEC in the YEB increased significantly from 2000 to 2017. (3) There was an alternating change from decoupling to coupling and then to negative decoupling from 2000 to 2017. Based on the conclusions mentioned above, it is proposed that the formulation of low-carbon agricultural development strategies should consider the structural adjustment of agricultural energy consumption and the advancements of agricultural technology.

Transcatheter closure of muscular ventricular septal defects using the Cardi-O-Fix plug.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the Cardi-O-Fix plug used for the treatment of muscular ventricular septal defects. METHODS: We retrospectively reviewed the medical records of five patients with muscular ventricular septal defects who underwent transcatheter closure using the Cardi-O-Fix Plug, from November 2017 to August 2019. The median age was 5.1 years (range: 3.2-6.5). Their median body weight was 18.1 kg (range: 13.4-21.8). All the patients underwent detailed two-dimensional Doppler and colour flow imaging by transthoracic echocardiography. The left ventricular median defect size of the muscular ventricular septal defects was 5.6 mm (range: 5.3-7.0). The right ventricular median defect size of the muscular ventricular septal defects was 3.9 mm (range: 3.3-4.7). All the procedures were performed on beating hearts. RESULTS: All the patients underwent successful device implantation with no displacement or detachment, they have complete echocardiographic closure at the 1-year follow-up. There were no occluder-related arrhythmia, chordae tendineae rupture, tricuspid insufficiency, aortic regurgitation, haemolysis, or embolisation. CONCLUSIONS: Application of the Cardi-O-Fix plug appears to be a feasible, safe, and effective treatment option for patients with muscular ventricular septal defects. Longer follow-up periods are warranted to prove the conclusion for long-term outcomes.

Butyrate pretreatment attenuates heart depression in a mice model of endotoxin-induced sepsis via anti-inflammation and anti-oxidation.

OBJECTIVES: The depressed heart function is the main complication to cause death of septic patients in clinic. It is urgent to find effective interventions for this intractable disease. In this study, we investigated whether butyrate could be protective for heart against sepsis and the underlying mechanism. METHODS: Mice were randomly divided into three groups. Model group challenged with LPS (30 mg/kg, i.p.) only. Butyrate group received butyrate (200 mg/kg·d) for 3days prior to LPS administration (30 mg/kg). Normal group received saline only. 6h and 12h after LPS administration were chosen for detection the parameters to estimate the effects or mechanism of butyrate pretreatment on heart of sepsis. RESULTS: The data showed that septic heart depression was attenuated by butyrate pretreatment through improvement of heart function depression (P<0.01) and reduction of morphological changes of myocardium. The overexpression of proinflammatory factors, TNF-α, IL-6 and LTB4, in heart tissues induced by sepsis was significantly alleviated by butyrate pretreatment (P<0.01). As oxidative stress indicators, SOD and CAT activity, and MDA content in heart were deteriorated by LPS challenge, which was noticeably ameliorated by butyrate pretreatment (P<0.01 or P<0.05). CONCLUSIONS: In conclusion, pretreatment with butyrate attenuated septic heart depression via anti-inflammation and anti-oxidation.

IKKα-mediated signaling circuitry regulates early B lymphopoiesis during hematopoiesis.

Multiple transcription factors regulate B-cell commitment, which is coordinated with myeloid-erythroid lineage differentiation. NF-κB has long been speculated to regulate early B-cell development; however, this issue remains controversial. IκB kinase-α (IKKα) is required for splenic B-cell maturation but not for BM B-cell development. In the present study, we unexpectedly found defective BM B-cell development and increased myeloid-erythroid lineages in kinase-dead IKKα (KA/KA) knock-in mice. Markedly increased cytosolic p100, an NF-κB2-inhibitory form, and reduced nuclear NF-κB p65, RelB, p50, and p52, and IKKα were observed in KA/KA splenic and BM B cells. Several B- and myeloid-erythroid-cell regulators, including Pax5, were deregulated in KA/KA BM B cells. Using fetal liver and BM congenic transplantations and deleting IKKα from early hematopoietic cells in mice, this defect was identified as being B cell-intrinsic and an early event during hematopoiesis. Reintroducing IKKα, Pax5, or combined NF-κB molecules promoted B-cell development but repressed myeloid-erythroid cell differentiation in KA/KA BM B cells. The results of the present study demonstrate that IKKα regulates B-lineage commitment via combined canonical and noncanonical NF-κB transcriptional activities to target Pax5 expression during hematopoiesis.

Study on compaction characteristics and mechanical model of dry crushing filling material under lateral confinement condition.

The compaction characteristics and bearing capacity of dry filling materials in goaf have a significant influence on stope control and surface stability. Through acoustic emission monitoring and mechanical model analysis, a series of confined compression tests were conducted on crushed waste with varying particle sizes and Talbot coefficients. The deformation, fragmentation, and acoustic emission characteristics under corresponding working conditions were determined. The results indicate that the stress-strain curves of crushed stone with different particle sizes and Talbot coefficients exhibit similar nonlinear behavior during confined compression. However, the strain response varies with changing stress levels. By analyzing the slope change rate of the stress-strain curve, the lateral uniaxial compression process of waste rock can be divided into three deformation stages: rapid compression, stable crushing, and slow compaction. The compressive deformation characteristics of gravel differ based on particle size and Talbot coefficient. Specimens with a higher Talbot coefficient demonstrate stronger compressive resistance and weaker deformation resistance during initial compaction loading. Notably, the internal pressure structure strength is influenced by factors such as maximum particle size D, grading coefficient n, and particle size distribution continuity, rather than solely by the proportion of large particles. The evolution of acoustic emission signals and energy-time curve during waste rock confined axial compression synchronizes with the compaction process. Overall, compaction plays a critical role in maintaining the stability of goaf in dry crushed waste filling.

Incentive policy for the comprehensive development of young medical talents: an evolutionary game study.

Introduction: Currently in China, there is a lack of well-defined and viable incentive mechanisms at the governmental and hospital levels to support the development of young medical talents, thereby hindering their growth Existing studies primarily investigate the current state and trajectory of incentives, yet they inadequately address the distinctive characteristics of various stakeholders involved in medical talent incentive processes, particularly the lack of research on incentive mechanisms with Chinese attributes. Methods: This study adopts evolutionary game theory to investigate the dynamics of replication and the strategies for achieving evolutionary stability in the comprehensive development of young medical talents, considering both scenarios with and without supportive policies. Results: In the absence of any supportive policy measures, the evolutionarily stable strategy (ESS) point is O(0,0), the unstable equilibrium point is C(1,1), and the saddle points are A(0,1), B(1,0). The initial state of the system is at the unstable equilibrium point C(1,1), which means that the young medical talents and medical institutions adopt a combination of strategies (actively seeking comprehensive development and taking incentive measures). Under the scenario with supportive policies, the ESS point is C(1,1), the unstable equilibrium point is O(0,0), and the saddle points are A(0,1), B(1,0). The initial state of the system is at the unstable equilibrium point O(0,0), which means that young medical talents and medical institutions adopt (N,N) strategy combinations (inactively seeking comprehensive development, implementing no incentive measure). Discussion: (1) Government incentives play a crucial role in motivating young medical talents to seek comprehensive development. (2) The level of government incentive support for young medical talents should exceed the cost increment of individual efforts. Additionally, the policy support provided by the government to medical institutions should surpass the incentive support offered by these institutions to young medical talents. This will enhance the motivation and encouragement efforts of medical institutions in actively promoting comprehensive development among young medical talents. (3) With the backing of certain government incentive policies, medical institutions implementing incentive measures and young medical talents actively seeking comprehensive development will establish a virtuous cycle of mutual promotion.

Puerarin Ameliorated PCOS through Preventing Mitochondrial Dysfunction Dependent on the Maintenance of Intracellular Calcium Homeostasis.

Polycystic ovarian syndrome (PCOS) is the major cause of infertility in reproductive women, but no universal drug is feasible. Although puerarin clinically treats cerebrovascular and cardiovascular diseases, its curative effect on PCOS remains elusive. The present study discovered that administration of puerarin restored estrous cycle of PCOS mice and diminished the number of cystic follicles with the concomitant recovery for circulating testosterone, LH and FSH levels, and LH/FSH ratio, indicating the therapeutic role of puerarin in PCOS. KEGG analysis of differential genes between PCOS and control revealed the enrichment in MAPK and calcium signaling pathway. Application of puerarin restricted the phosphorylation of ERK1/2 and JNK, whose activation neutralized the improvement of puerarin on the secretory function and apoptosis of ovarian granulosa cells (GCs). Meanwhile, puerarin alleviated the accumulation of cytosolic Ca2+ through restricting the opening of Ryr and Itpr channels, but this effectiveness was counteracted by the activatory ERK1/2 and JNK. Attenuation of cytosolic Ca2+ counteracted the antagonistic effects of ERK1/2 and JNK activation on puerarin's role in rescuing the calcineurin and Nfatc. Further analysis manifested that Mcu had been authenticated as a direct downstream target of Nfatc to mediate the amelioration of puerarin on mitochondrial Ca2+ uptake. Moreover, puerarin prevented the disorder of ATP content, mitochondrial membrane potential, and mitochondrial permeability transition pore opening through maintaining mitochondrial Ca2+ homeostasis. Collectively, puerarin might ameliorate the symptoms of PCOS mice through preventing mitochondrial dysfunction that is dependent on the maintenance of intracellular Ca2+ homeostasis after inactivation of ERK1/2 and JNK.

Development and validation of a questionnaire to measure the congenital heart disease of children's family stressor.

Background: Families of children with congenital heart disease (CHD) face tremendous stressors in the process of coping with the disease, which threatens the health of families of children with CHD. Studies have shown that nursing interventions focusing on family stress management can improve parents' ability to cope with illness and promote family health. At present, there is no measuring tool for family stressors of CHD. Methods: The items of the scale were generated through qualitative interviews and a literature review. Initial items were evaluated by seven experts to determine content validity. Factor analysis and reliability testing were conducted with a convenience sample of 670 family members. The criterion-related validity of the scale was calculated using scores on the Self-Rating Anxiety Scale (SAS). Results: The CHD Children's Family Stressor Scale consisted of six dimensions and 41 items. In the exploratory factor analysis, the cumulative explained variance of the six factors was 61.085%. In the confirmatory factor analysis, the six factors in the EFA were well validated, indicating that the model fits well. The correlation coefficient between CHD Children's Family Stressor Scale and SAS was r = 0.504 (p < 0.001), which indicated that the criterion-related validity of the scale was good. In the reliability test, Cronbach's α coefficients of six sub-scales were 0.774-0.940, and the scale-level Cronbach's α coefficient value was 0.945. Conclusion: The study indicates that the CHD Children's Family Stressor Scale is valid and reliable, and it is recommended for use in clinical practice to assess CHD children's family stressors.

Intrinsic targeting of host RNA by Cas13 constrains its utility.

Cas13 can be used for the knockdown, editing, imaging or detection of RNA and for RNA-based gene therapy. Here by using RNA immunoprecipitation sequencing, transcriptome profiling, biochemical analysis, high-throughput screening and machine learning, we show that Cas13 can intrinsically target host RNA in mammalian cells through previously unappreciated mechanisms. Different from its known cis/trans RNA-cleavage activity, Cas13 can also cleave host RNA via mechanisms that are transcript-specific, independent of the sequence of CRISPR RNA and dynamically dependent on the conformational state of Cas13, as we show for several Cas13-family effectors encoded in one-vector and two-vector lentiviral systems. Moreover, host genes involved in viral processes and whose transcripts are intrinsically targeted by Cas13 contribute to constraining the lentiviral delivery and expression of Cas13. Our findings offer guidance for the appropriate use of lentiviral Cas13 systems and highlight the need for caution regarding intrinsic RNA targeting in Cas13-based applications.

Nitrogen-coordinated antimony atom anchored on carbon matrix as efficient active sites to enhance sodium/potassium ion storage.

Carbon-based anode materials have become a research hotspot for alkali metal ion batteries. Crucially, the electrochemical performance of carbon materials must be improved by appropriate means such as micro-nano structure design and atomic doping. Herein, antimony doped hard carbon materials are prepared by anchoring Sb atoms on nitrogen-doped carbon (SbNC). The coordination of non-metal atoms can better disperse Sb atoms on the carbon matrix, and the synergistic effect between Sb atoms, coordinated non-metal atoms, and hard carbon matrix endows SbNC anode with good electrochemical performance. When used in sodium-ion half-cells, the SbNC anode showed high rate capacity of 109 mAh g-1 at 20 A g-1 and good cycling performance (254 mAh g-1 at 1 A g-1 after 2000 cycles). In addition, when used in potassium-ion half-cells, the SbNC anode exhibited initial charge capacity of 382 mAh g-1 at 0.1 A g-1 and rate capacity of 152 mAh g-1 at 5 A g-1. This research shows that compared with ordinary nitrogen doping, Sb-N coordination active sites on carbon matrix can provide much more adsorption capacity, improve ion filling and diffusion properties as well as enhance the kinetics of electrochemical reaction for the sodium/potassium storage.

Families under pressure: A qualitative study of stressors in families of children with congenital heart disease.

The objective of this study was to better understand the stressors in families of children with congenital heart disease (CHD) to assist with formulating targeted stress management plans for such families. A descriptive qualitative study was undertaken at a tertiary referral hospital in China. Following purposeful sampling, interviews were conducted with 21 parents of children with CHD regarding the stressors in their families. Following content analysis, 11 themes were generated from the data and categorised into six main domains: the initial stressor and associated hardships, normative transitions, prior strains, the consequences of family efforts to cope, intrafamily and social ambiguity, and sociocultural values. The 11 themes include confusion regarding the disease, hardships encountered during treatment, the heavy financial burden, the unusual growth track of the child due to the disease, normal events becoming abnormal for the family, impaired family functioning, family vulnerability, family resilience, family boundary ambiguity induced by role alteration, a lack of knowledge about community support and family stigma. Various and complex stressors exist for families of children with CHD. Medical personnel should fully evaluate the stressors and take targeted measures before implementing family stress management practices. It is also necessary to focus on the posttraumatic growth of families of children with CHD and strengthen resilience. Moreover, family boundary ambiguity and a lack of knowledge about community support should not be ignored, and further research is needed to explore these variables. Most importantly, policymakers and healthcare providers should adopt a range of strategies to address the stigma of being in a family of a child with CHD.

[Catheter directed thrombolysis for early left lower extremity deep venous thrombosis without vena cava filters protection].

OBJECTIVE: To investigate the indications, safety and efficacy of catheter directed thrombolysis for early left lower extremity deep venous thrombosis (DVT) without vena cava filters protection. METHODS: Clinical data of 54 cases of early left lower extremity DVT received catheter directed thrombolysis without vena cava filters from July 2008 to June 2010 were retrospectively analyzed. The thrombosis was entire without free floating clots and no thrombosis in vena cava detected with ultrasound scan. Twenty-five patients were male and 29 were female with the average age of 52.8 years. Fifty-one of which were iliofemoral and popliteal, the other 3 were iliofemoral. The course were ≤ 7 d in 45 cases and these were 8 to 30 d in 9 cases. Urokinase of 300 000 U was infused through catheters per 2 h twice a day. Meanwhile 4000 U of low weight heparin was administered subcutaneously per 12 h, or heparin infusion at dosage of 18 U×kg(-1)×h(-1). RESULTS: The procedure technically succeeded in all patients. In total cases venous score decreased to 4.6 ± 2.1 post 6 to 10 d of thrombolysis from 10.8 ± 1.0 with thrombolysis rate of 58% ± 18% which was not significantly different between groups of ≤ 7 d and 8 to 30 d (t = 1.02, P = 0.34). On 14(th) day, 11 patients (20.4%) completely recovered, 35 cases (64.8%) experienced large improvement, 8 patients (14.8%) had mild improvement and nobody was failed, resulting in total efficacy of 100%. No patient developed clinical symptomatic pulmonary embolism. SpO2 did not alter markedly post thrombolysis [(91.0 ± 2.6)% vs. (90.8 ± 2.4)%, t = 2.03, P = 0.05]. No patients suffered from cerebral hemorrhage and haemoturia, and catheter induced inflammation occurred in 4 cases (7.41%). There was mild bleeding in puncture sites in 11 patients (20.4%) during the course. There were 36 patients (66.7%) had been followed up with the time of 6 to 21 months. In which 31 cases had no lower extremity edema or had mild edema after activities. Two patients developed serious edema after activities for deep venous insufficiency. Three cases combined with malignant tumor or renal failure recurred. CONCLUSIONS: For early left extremity DVT which is entire without free floating clots and no thrombosis in vena cava, catheter directed thrombolysis without filter protection maybe administered with safety, efficiency and lower expense.

A Four-Stepwise Electrocardiographic Algorithm for Differentiation of Ventricular Arrhythmias Originated from Left Ventricular Outflow Tract.

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

Polysaccharide-protein complex from Lycium barbarum L. is a novel stimulus of dendritic cell immunogenicity.

Dendritic cell (DC) immunogenicity correlates with its maturation, which can be induced by toxic microbial products such as LPS. In this study, we report that a nontoxic polysaccharide-protein complex isolated from a Chinese medicinal herb, Lycium barbarum (LBP), induces phenotypic and functional maturation of DCs with strong immunogenicity. LBP up-regulated DC expression of CD40, CD80, CD86, and MHC class II molecules; down-regulated DC uptake of Ag; enhanced DC allostimulatory activity; and induced IL-12p40 and p70 production. All of its five fractions were active. LBP developed enhanced Th1 response, and LBP-treated DCs enhanced Th1 and Th2 responses in vitro and in vivo. Our study provides evidence and rationale on using LBP in various clinical conditions to enhance host immunity and suggests LBP as a potent adjuvant for the design of DC-based vaccines.

Deal or no deal on water-saving program? Exploring the optimal interval for government subsidies and internal incentives.

Water resources can be soon exhausted with the overdeveloped industrialization. High-water-consumption (HWC) industries and their supply chains are trying to reduce water consumption in the production process. These water-saving behaviors and effects may be subsidized by the government to pursue the goal of social welfare maximization (SWM). In this context, to investigate when to bring in government subsidy for any water-saving behaviors and effects to maximize the social welfare, six game-theoretical decision models for the water-saving supply chain under three scenarios are developed, analyzed, and compared, and the corresponding numerical and sensitivity analyses of water-saving case in the papermaking industry are conducted and compared; on this basis, the corresponding policy implications and managerial insights are discussed and summarized in this article. The research results indicate that the supply chain would only have internal incentive to implement water-saving management under low- or medium-cost case, while the government would only have external incentive to subsidize water-saving behaviors and effects under medium-cost case. Besides, the coordination strategy outperforms the equilibrium strategy regarding the water-saving effects, operational performances, social welfare, consumer surplus, and positive externality for the water-saving supply chain under all three scenarios. Furthermore, a kind of niche targeting subsidy policy based on actual water-saving effect that the government only subsidizes the water-saving supply chain operating under coordination strategy with medium water-saving cost structure can achieve social welfare maximization, operational performance improvement, and positive externality enhancement. PRACTITIONER POINTS: The optimal interval for internal incentives of water-saving is explored. The optimal interval for government subsidies of water-saving is investigated. The optimal operational strategy for the water-saving supply chain is examined.

CKAP4 participates in tryptase-induced phenotypic conversion in atrial fibroblasts through PAR2/p38/JNK pathway.

Our previous study found that tryptase activated atrial fibroblasts, increased collagen synthesis in atrial fibroblasts through protease activated receptor-2 (PAR2) receptors. Recent studies showed that cytoskeleton-associated protein 4 (CKAP4) played an important role in ventricular fibroblast activation. The present study aimed to investigate the role of CKAP4 in tryptase-induced atrial fibroblast activation, atrial fibrosis, and molecular regulatory mechanisms. We cultured atrial fibroblasts in vitro, gave cells tryptase stimulation, then overexpressed or silenced PAR2 and CKAP4 genes in the cells. Their effects on atrial fibroblast proliferation, migration, extracellular matrix remodeling (Collagen I and fibronectin) and downstream key molecules (TGF-ß1, c-jun and c-fos, JNK, p38) were investigated. The results showed that the expression of CKAP4 was significantly increased by tryptase and further increased by pcDNA3.1-PAR2, but decreased by FALLRY-NH2 and PAR2 siRNA. CKAP4 overexpression significantly increased the cell proliferation, migration and levels of Collagen I and fibronectin, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in atrial fibroblasts, while CKAP4 siRNA significantly reduced them. CKAP4 overexpression significantly increased the expression of TGF-ß1, c-jun and c-fos, and activated the JNK/p38 pathway, which were suppressed by CKAP4 siRNA. In conclusion, CKAP4 is involved in tryptase-induced phenotypic conversion in atrial fibroblasts through PAR2/p38/JNK pathway, which may provide novel targets in the prevention of atrial fibrosis.